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Как искусственный интеллект  помогает лечить рак почек. Патология, диагностика, прогноз (часть 2)

Привет, это команда МедТех ИИ и дирекции по искусственному интеллекту и цифровым продуктам билайна и врачи-учёные из Сеченовского университета. И это вторая часть нашей статьи из журнала Biomedicines про применение искусственного интеллекта в диагностике рака почки. Первую часть можно прочитать тут.

Дифференциальный диагноз почечно-клеточной карциномы

Для достоверной диагностики и наблюдения за пациентами с различными типами почечно-клеточной карциномы (ПКК) необходимо точно определить гистологический вариант опухоли. Задача представляет собой дифференцирование между основными типами рака почки. Эту проблему тоже можно решить с помощью цифровой патологии. Внедрение искусственного интеллекта в рутинную гистопатологию позволит использовать дополнительные методы анализа для определения гистологического типа рака еще до того, как патологоанатом поставит точный диагноз, что значительно ускорит диагностический процесс.

Рис. 3. Дифференциальная диагностика гистологических типов рака почки (светлоклеточный, папиллярный и хромофобный почечно-клеточный рак).
Рис. 3. Дифференциальная диагностика гистологических типов рака почки (светлоклеточный, папиллярный и хромофобный почечно-клеточный рак).

Помимо достоверного установления гистологического типа рака, важной проблемой является дифференциация злокачественных и доброкачественных опухолей. Эта проблема является значимой для онкоцитомы и хПКК, а также для метанефрической аденомы и пПКК. В одной из публикаций Чорди и другие авторы проанализировали 48 гистологических сканов (По 12 снимков для каждого гистологического типа опухоли - светлоклеточной, папиллярной, хромофобной ПКК и онкоцитомы). Сканы были преобразованы в четырехуровневые изображения в оттенках серого, а затем выполнена сегментация. Различные признаки были извлечены из изображений ПКК и использованы для корректной классификации гистологических подтипов. Классификация была выполнена с точностью более 90% с помощью простого многоклассового байесовского классификатора, предполагающего многомерные распределения Гаусса. В аналогичном исследовании авторы отказались от сегментации и использовали метод углов Харриса для локализации ключевых точек на 48 сканах четырех типов опухолей почек. Точность байесовского классификатора достигла 83%.

Менгдан Чжу и др. разработали глубокую нейросетевую модель, которая может точно классифицировать оцифрованные сканы гистологических образцов после хирургической резекции и биопсии на пять групп: светлоклеточная ПКК, папиллярная ПКК, хромофобная ПКК, онкоцитома почки и нормальная ткань. Показатели для данных из «Атласа генома рака» составили 0,98 (95% доверительный интервал (ДИ): 0,97-1,00), 0,98 (95% ДИ: 0,96-1,00) и 0,97 (95% ДИ: 0,96-1,00), (95% ДИ: 0,96-0,98), соответственно.

Также важным является обучение нейронной сети распознаванию доброкачественных почечных поражений. Авторы собрали набор гистологических сканов со следующими типами опухолей почек: светлоклеточная ПКК (сПКК), папиллярная ПКК (пПКК), хромофобная ПКК (хПКК), светлоклеточная папиллярная ПКК (спПКК), онкоцитома и метанефрическая аденома.

Затем был построен классификатор с использованием Google AutoML Vision, коммерческого интерфейса прикладного программирования для разработки классификаторов изображений на основе ИИ. После 1 часа обучения средняя точность классификатора составила 76% (площадь под кривой "точность-отдача"). Затем классификатор обучался в течение 8 часов, и средняя точность итоговой модели составила 93%. Классификатор правильно идентифицировал 47/55 (85%) случаев (сПКК 11/13, пПКК 14/15, хПКК 10/11, спПКК 2/4, онкоцитома 8/9 и метанефрическая аденома 2/3). Все опухоли с коэффициентом более 0,77 были правильно классифицированы.

В другой публикации авторы создали фреймворк, состоящий из трех конволюционных нейронных сетей. На сканах ПКК выделялись патчи разного размера (малый размер = 250 × 250, средний размер = 350 × 350 и большой размер = 450 × 450) , далее отдельная нейронная сеть обрабатывала участок определенного размера. На гистологических сканах были выделены четыре типа тканей: жировая, паренхима почки, сПКК и пПКК. Фреймворк успешно классифицировал четыре класса и продемонстрировал высокую производительность по сравнению с современными методами (пиксельная точность: 0,89 по ResNet18; предложенная: 0,89 по ResNet18 предложенная: 0.92).

Различная экспрессия и локализация иммуногистохимических маркеров в подтипах рака почки может иметь значение к прогрессированию опухоли и ответу на таргетную терапию. Экспрессия некоторых антител может предсказывать исход заболевания и указывать на злокачественность (PD-L1, Ki-67). Другие антитела могут использоваться в качестве маркеров васкуляризации (CD31) и инфильтрации тканей различными типами иммунных клеток (CD3, CD8, CD20, CD68), что также имеет важное прогностическое значение.

В одном из исследований авторы изучали микроокружение при различных типах рака почки, а также сравнивали образцы тканей с метастазами или рецидивами (n = 15). Всего было проанализировано 83 опухоли почки: оба типа пПКК (n = 20) и (n = 49), карцинома собирательных трубочек (n = 14) и уротелиальная карцинома высокой степени злокачественности (HGUC; n = 5). С помощью машинного обучения был проведен анализ 10 различных маркеров на сканах иммуногистохимических препаратов из разных опухолей, включая маркеры мезенхимальной ткани, иммунной инфильтрации и эндотелия, а также клеточной пролиферации. Для выявления мембранной и/или цитоплазматической экспрессии CD68, CD163, CD3, CD8, CD20 и виментина был обучен классификатор HALO random forest с использованием алгоритма HALO Area quantification v1.0.

Для определения антител к CD31, Ki67 и PDL1 использовался алгоритм object colocalization v1.2. Этот алгоритм выявлял положительно окрашенные клетки или объекты на основе их размера и формы и определял общее количество положительно окрашенных объектов на 1 мм2 площади. Алгоритмы оценки Ki-67 и виментина были обучены на всей ткани. В обучение включались как опухолевые, так и неопухолевые участки. Процент площади положительного маркера рассчитывался путем деления площади положительного окрашивания на общую площадь ткани и умножения на 100. После статистического анализа иммунные маркеры показали различный уровень экспрессии при разных гистологических типах рака: количество CD3+ Т-клеток и CD20+ В-клеток было статистически значимо выше в CDC. CD68+ макрофаги преобладали в пПКК 1-го типа. PD-L1 был значительно повышен в метастатических образцах. Экспрессия Ki-67 была ниже в пПКК 1-го типа, чем в пПКК 2-го типа (IRR = 0,47, 95% CI = 0,21-0,92, p = 0,017). Эти выводы позволили получить новое представление о природе редких видов рака почки, которые часто остаются недостаточно изученными.

Для улучшения диагностики некоторые исследователи использовали нейронные сети, предварительно обученные диагностировать различные опухоли. Например, Кевин Фауст и др. применили свёрточную нейронную сеть (СНС), предварительно обученную распознавать гистоморфологию опухолей головного мозга , к 550 цифровым изображениям двух типов почечно-клеточной карциномы (396 сПКК, 154 пПКК). В общей сложности было извлечено 512 различных признаков для кластеризации набора изображений и анализа клинической и биологической значимости, возникающей между подгруппами пациентов. Примечательно, что СНС, предварительно обученные на больших гистологических наборах данных, могут распространить изученные представления на новые патологии, устраняя клинически значимые различия в структуре тканей внутри и между пациентами без дополнительной оптимизации.

Обученные гистологические модели могут быть доработаны и использованы для оценки прогноза. Это делает их не только диагностическими, но и прогностическими. В исследовании авторы обучили СНС на гистологических сканах из «Атласа генома рака» распознавать опухолевую ткань от нормальной, а затем определять гистологический тип опухоли (светлоклеточная, папиллярная и хромофобная ПКК) с точностью 87,69%. Используя СНС-модель, дифференцирующую ПКК от нормальной ткани, авторы определили места расположения опухолей с высокой вероятностью риска и построили тепловую карту вероятности.

На основе участков опухоли из скан-изображений каждого ПКК были извлечены некоторые характеристики формы опухоли и ядер, такие как площадь и периметр. Индекс риска для каждого пациента рассчитывался с помощью регуляризованной модели Кокса-ЛАССО для каждого признака и проверялся с помощью двухэтапной процедуры перекрестной валидации. Было установлено, что тринадцать характеристик морфологии раковых клеток и шесть характеристик ядерной морфологии значимо связаны с выживаемостью пациентов (p-value < 0,05).

Нейронные сети могут быть многозадачными, например, их можно обучить распознавать как опухолевые, так и нормальные ткани, определять гистологический тип опухоли и ее класс, а также оценивать прогноз заболевания. Чемпион и другие авторы классифицировали гистологические сканы различных типов ПКК на основании четырех классаов Фурман на основе цвета и текстуры ядер. Учитывались также форма и топологические особенности ядер. Выборка состояла из 47% сПКК, 33% пПКК и 20% хПКК; всего было использовано 160 сканов. Из каждого изображения методом бинарной сегментации было извлечено 1316 цветовых, текстурных, формальных и топологических признаков для каждого типа рака. После обучения и валидации эта модель классифицировала различные изображения ПКК по четырем классам согласно классификации Фурман с точностью 90,4%.

Другие исследователи разработали СНС, которая различала типы рака почки и нормальной ткани, а также классифицировала опухоль по Фурман. Модель достигла общей точности 99,1% для различения нормальной паренхимы и ПКК в выборке (чувствительность 100%, специфичность 97,1%). Точность дифференцировки светлоклеточного, папиллярного и хромофобного гистотипов ПКК составила 97,5%. Точность классификации по Фурман составила 98,4%. Поскольку применимость классификации Фурман к хПКК остается спорной, многие патоморфологи в своей практике предпочитают использовать классификацию Панера.

Светлоклеточная ПКК

Светлоклеточная почечно-клеточная карцинома (сПКК) — это морфологически гетерогенная злокачественная опухоль, происходящая из клеток почечного канальцевого эпителия. Опухолевые клетки имеют преимущественно прозрачную, иногда эозинофильную цитоплазму и окружены обильной сетью кровеносных сосудов. сПКК - наиболее распространенный тип ПКК у взрослых, составляющий 60-75% всех ПКК. Большинство случаев сПКК развивается спорадически, т.е. отсутствуют известные наследственные предрасполагающие факторы. Диагноз обычно ставится случайно, например, при проведении медицинских визуализационных исследований, не связанных с заболеваниями почек. Метастазы обнаруживаются у 25% пациентов, их выживаемость составляет от 6 до 12 месяцев. В 70-90% всех случаев сПКК наблюдаются определенные патологические изменения в длинном плече третьей хромосомы - сегменте 3p. Часто обнаруживается инактивация гена болезни фон Хиппеля-Линдау, связанная с миссенс-мутацией и/или гиперметилированием промотора этого гена.

Наиболее важным параметром, связанным с прогнозом заболевания, является классификация. С этой целью при сПКК оцениваются ядра опухолевых клеток. Ранее использовалась четырехуровневая классификация Фурман, основанная на ядерной морфологии и визуализации ядрышка. Современная классификация WHO/ISUP также состоит из четырех классов. Иногда для упрощения рабочего процесса предлагается использовать двухэтапные классификации. В большинстве рассмотренных нами публикаций сПКК разделяется на две большие группы в зависимости от класса: высокодифференцированные (первый и второй классы по Фурман) и низкодифференцированные (третий и четвертый классы по Фурман).

В одном из исследований авторы создали нейронную сеть для распознавания высоко- и низкодифференцированного рака с использованием классификации Фурман. Они обучили модель прогнозирования выживаемости пациентов на основе эпидемиологических и клинических данных. После обработки данных 42 пациентов была создана ЛАССО-модель, включающая 26 различных признаков. Чувствительность и специфичность составили 84,6% и 81,3% соответственно. Затем исследователи применили эту модель к 160 случаям сПКК, используя данные о возрасте, поле, классе опухоли, стадии по TNM и лечении для оценки прогноза заболевания.

Рис.5. Обнаружение ядер и сегментация при низко- и высокодифференцированном светлоклеточном почечно-клеточном раке (сПКК).
Рис.5. Обнаружение ядер и сегментация при низко- и высокодифференцированном светлоклеточном почечно-клеточном раке (сПКК).

Также можно определить высокий и низкий класс опухоли, автоматически оценив размер ядер. Используя пространственное распределение размеров ядер, авторы создали тепловую карту и определили диаметр ядра, характерный для каждого класса. Они также показали, что средний размер ядра в сканах высокозлокачественного рака составляет 6 мкм, а низкозлокачественного рака - 9 мкм. Исследователи использовали алгоритм автоматического распознавания цвета, встроенный в программу WS-Recognizer, и машину опорных векторов в качестве классификатора. Для обучения классификатора программа производила выборку красных, синих и зеленых пикселей. Крук и др. разработали нейросеть и продемонстрировали автоматическую градацию при сПКК по классификации Фурман. Точность определения составила 96,7%, а чувствительность и специфичность для каждой градации были различными и составляли от 87,3 до 99,3%.

Другие исследователи создали автоматизированный механизм классификации изображений для разделения сПКК на две группы в зависимости от степени злокачественности. Для анализа ядер и визуализации ядрышка использовались методы машинного обучения и извлечения признаков на основе интенсивности пикселей изображения. С помощью двух отдельных детекторов программа генерировала два набора выделенных областей изображения ядрышек. Затем программа проводила количественную оценку плеоморфных паттернов ядер, объединив признаки, извлеченные из нескольких областей изображения с ядром.

Технологии машинного обучения могут помочь в прогнозировании рака почки и потенциально улучшить клиническое лечение этого заболевания. Компьютерная программа на основе искусственного интеллекта может прогнозировать выживаемость пациентов с раком почки, одновременно анализируя различные медицинские данные (микроскопические изображения, снимки КТ/МРТ и геномные данные). Для этого автор Мариен и другие создали комплексную мультимодальную модель глубокого обучения (КМ МГО), состоящую из отдельных 18-слойных остаточных нейронных сетей для каждой модели изображения и геномных данных. Сначала нейронная сеть была обучена на гистологических снимках, затем к обучению были добавлены снимки КТ и МРТ и геномные данные. Всего было проанализировано 113 пациентов с точностью 83,43 % ± 11,62 % с максимальным значением 100 % при 12-кратной перекрестной валидации.

Исследователи продемонстрировали, что оценка изображений, используемая в программе, коррелирует (R = 0,59) с существующей системой оценки, основанной на мультигенном анализе, - ключевым прогностическим показателем для пациентов с сПКК. В другой публикации было показано, что патологическая сигнатура, основанная на машинном обучении, может служить новым прогностическим маркером для пациентов с сПКК. Авторы провели выявление и сегментацию ядер при сПКК с помощью программного обеспечения для цифровой патологии QuPath на трех разных выборках пациентов. Определялись морфологические особенности опухолевых клеток, ядра и цитоплазмы.

Для определения оптимальных характеристик цифровой патологии и расчета коэффициентов для каждого признака в модели использовался пакет Glmnet, который позволял проводить наименьшее абсолютное сжатие и отбор. Среднее время наблюдения за пациентами этих выборок составило 26,4 ± 16,8, 54,9 ± 27,8 и 43,2 ± 30,6 мес. соответственно. Для ЛАССО-анализа были выбраны следующие прогностические факторы: округлость ядра, минимальный размер ядра, средняя оптическая плотность гематоксилина ядра, минимальный размер гематоксилина ядра и стандартное отклонение размера эозина клеток. Эти признаки были включены в разработку многослойной перцептронной системы (МПС). Регрессионный анализ по методу Кокса показал, что МПС может быть использована в качестве независимого прогностического фактора выживаемости пациентов с сПКК. Интегрированная номограмма, основанная на МПС, системе стадирования опухоли и системе балльной оценки злокачественности, повысила текущую точность прогнозирования выживаемости пациентов с сПКК: значения площади под кривой составили 89,5%, 90,0%, 88,5% и 85,9% для прогнозирования выживаемости через 1, 3, 5 и 10 лет после постановки диагноза.

Прогнозирование прогрессирования почечной патологии может быть также основано на оценке васкуляризации, размеров некротических участков и других гистоархитектурных особенностей. Некроз ассоциируется с худшим прогнозом. Плотность сосудов в опухоли коррелирует с инвазивностью и гематогенным метастазированием. Для упрощения обнаружения сосудов часто используется иммуногистохимическое окрашивание антителами к эндотелию и оцифровка этих препаратов. В одном из исследований был разработан алгоритм для оценки связи между экспрессируемыми генами и морфологией кровеносных сосудов. Были разработаны два инструмента машинного обучения: один - для идентификации эндотелиальных клеток, другой - для определения границ сосудов и периваскулярных областей.

Для автоматизации аннотации ядер эндотелиальных клеток и повышения точности метода машинного обучения авторы применили информацию о типе клеток из иммуногистохимических препаратов гематоксилин-эозиновым изображениям точно такого же участка ткани. Затем была создана маска сосудистой области. Было обнаружено девять сосудистых признаков, предсказывающих выживаемость в выборке пациентов (n = 64, RR = 2,3). Две обобщенные линейные модели, основанные на 14 генах (14VF и 14GT), разделили пациентов на группы с хорошей и плохой выживаемостью (RR 14VF = 2,4, RR 14GT = 3,33).

Для прогностической оценки использовались также данные иммуногистохимических исследований с антителами, выявляющими опухолеинфильтрирующие лимфоциты, указывающие на злокачественный потенциал. Штенцель и другие исследовали экспрессию антител против опухолеинфильтрирующих CD3-положительных Т-клеток, CD8-положительных цитотоксических Т-лимфоцитов, регуляторных Т-клеток, В-клеток, плазматических клеток, макрофагов, гранулоцитов, рецептора программированной клеточной смерти-1 (PD-1) и его лиганда PD-L1 у большого числа пациентов с сПКК (n = 756). Препараты иммуногистохимии были оцифрованы и проанализированы с помощью платформы HALO. Для количественной оценки положительно окрашенных клеток и общего числа клеток в анализируемой области использовался цитоядерный модуль (v1.4e1.6), включающий тканевой классификатор для различения опухолевой и неопухолевой ткани.

Однофакторный анализ выживаемости показал, что увеличение количества инфильтрирующих опухоль В-клеток, Т-клеток и PD-1-позитивных клеток достоверно ассоциировалось с хорошим прогнозом, а высокий уровень внутриопухолевых гранулоцитов, макрофагов, цитотоксических Т-клеток и PD-L1 - с плохим прогнозом. Высокая инфильтрация цитотоксическими лимфоцитами или В-клетками и высокая экспрессия PD-L1 в клетках сПКК были квалифицированы как независимые прогностические биомаркеры. Далее авторы исследовали прогноз пациентов после терапии ниволумабом, изучив экспрессию иммунных клеток и PD-1/PD-L1.

Применение ИИ для исследования ряда молекулярных маркеров в каждом образце имеет прогностическое значение и может быть интегрировано с морфологическими признаками для улучшения стратификации риска и персонализированной терапии. В одном из исследований был разработан полуавтоматизированный метод исследования 62 маркеров и их комбинаций в 150 первичных раках с использованием мультиплексной иммунофлуоресценции, цифрового пространственного профилирования NanoString GeoMx и анализа изображений с помощью ИИ.

Анализ изображений проводился с помощью программы Definiens Tissue Studio, а анализ гистологических сканов - с помощью программы Indica Labs Halo AI. Как и в Tissue Studio, сегментация опухоли-стромы включала только участки опухоли, а сегментация ядер основывалась на интенсивности окрашивания Heochst. Было установлено, что совместная экспрессия маркеров стволовых клеток рака и эпителиально-мезенхимального перехода, таких как OCT4 и ZEB1, указывает на плохой исход. OCT4 и иммунные маркеры CD8, CD34 и CD163 значительно дифференцировали пациентов на промежуточной фазе лечения.

В литературе широко изучена взаимосвязь между гистологическими особенностями сПКК и генетическими и эпигенетическими данными, которые также успешно используются в качестве прогностических маркеров. Азуахе и другие авторы использовали машинное обучение, включая нейронные сети глубокого уровня, для изучения взаимосвязи между протеомикой и гистологическими сканами. На первом этапе с помощью классификатора случайного леса была построена диагностическая модель на основе протеомики. Выборка состояла из 997 белковых генных продуктов. Модель была способна дифференцировать нормальные образцы и образцы сПКК с общей точностью 0,98 и высокой чувствительностью и специфичностью (0,97 и 0,99 соответственно). На втором этапе была создана комплексно-архитектурную СНС, которая позволила отличить раковую опухоль от нормальной ткани почки с точностью 0,95 в тестовом наборе данных и высокой чувствительностью и специфичностью (1 и 0,93, соответственно). На третьем этапе обе модели были протестированы одновременно на 24 образцах (14 с раком почки и 10 с нормальной тканью). Затем модели были обучены анализу корреляции между данными протеомики и кодирующими их генами, а также между каждым набором данных и гистологическим прогнозом.

Искусственный интеллект может играть важную роль в диагностике редких подтипов заболеваний, выявляемых по генетическим изменениям. Почечно-клеточная карцинома с транслокацией TFE3 Xp11.2 (TFE3-ПКК) имеет более агрессивный характер роста, чем другие подтипы ПКК, однако TFE3-ПКК очень трудно диагностировать с помощью стандартной световой микроскопии. Для извлечения признаков из изображений был разработан автоматизированный вычислительный механизм. Было выявлено 52 признака, позволяющих отличить TFE3-ПКК от сПКК. Испытания классификационной модели на внешнем валидационном наборе показали высокую точность: площадь под ROC-кривой составила от 0,842 до 0,894. Кроме того, полученный результат продемонстрировал способность улавливать незначительные морфологические различия между TFE3-ПКК и сПКК и может существенно улучшить диагностику редких вариантов сПКК.

Папиллярная ПКК

Папиллярная почечно-клеточная карцинома (пПКК) возникает из эпителия дистальных извитых канальцев и составляет 10-15% всех случаев рака почки. пПКК - менее агрессивная опухоль, чем сПКК, с 5-летней выживаемостью 80-85%. пПКК - гетерогенное заболевание с двумя основными гистологическими подтипами. Опухоли первого типа состоят из сосочков и трубчатых структур, покрытых мелкими клетками с базофильной цитоплазмой и небольшими овальными ядрами. Опухоли второго типа состоят из сосочков, покрытых крупными клетками с эозинофильной цитоплазмой и крупными сферическими ядрами (с выступающими ядрышками). В некоторых случаях пПКК носит скрытый и мультифокальный характер. В других - имеет агрессивный летальный фенотип одиночных опухолей. Микроокружение опухоли играет очень важную роль в прогнозировании течения опухоли почки. Оно также позволяет указать гистологические биомаркеры. Оценка микроокружения опухоли при различных ее подтипах представляет собой интересную задачу.

В одном из исследований авторы предложили новый механизм для автоматизированной топологической характеристики клеточных структур в микроокружении опухоли. Эта программа была протестирована на большом общедоступном наборе гистопатологических изображений из выборки 190 пациентов с пПКК. Затем был проведен однофакторный анализ выживаемости по 50 морфологическим признакам и двум патологическим переменным (стадия TNM и подтип пПКК). Стадии II и III были объединены в одну группу и сравнивались с I стадией. Пациенты с пПКК 2-го типа имели худший прогноз, чем пациенты с 1-м типом.

Результаты эксперимента показали, что предложенные топологические признаки позволяют успешно разделять пациентов на ранних и средних стадиях заболевания с высокой выживаемостью. Эти результаты также продемонстрировали превосходство над традиционными клиническими признаками и морфологическими характеристиками клеток. Кроме того, площадь под кривой (AUC) прогноза бинарного 5-летнего выживания для стадии и подтипа составила 0,63 и 0,66, соответственно. Прогнозируемый индекс риска достиг AUC 0,78. Эти технологии не только дают новое представление о топологической организации раковых опухолей, но и могут быть интегрированы с геномными данными в будущих исследованиях для разработки новых комплексных биомаркеров.

Другим подходом к прогностической оценке является интеграция морфологических и генетических данных. В одной из публикаций авторы стремились всесторонне охарактеризовать иммунное микроокружение пПКК на основе анализа генетических данных, используя вычислительную биологию для анализа профильных данных. На основе мультиомиксного биоинформационного анализа авторы обнаружили, что пПКК обладает характеристиками "горячей" опухоли. Однако наличие CD8+ Т-клеток в опухолевой ткани не ограничивало ее прогрессию. Поэтому пациенты с пПКК могут получить большую клиническую пользу от лечения, направленного на устранение дефицита CD8+ Т-клеток.

Кроме того, экспрессия CCL5 и FASLG может быть связана с формированием иммуносупрессивного микроокружения в пПКК. Представленное в данной работе иммунное микроокружение дает новые представления для дальнейших экспериментальных и клинических исследований по индивидуализированной иммунотерапии пациентов с пПКК. Ле Ли и др. провели биоинформационный скрининг для изучения и идентификации потенциальных биомаркеров повреждения ДНК и окислительного стресса в пПКК. Данные секвенирования РНК были загружены из базы данных «Атласа генома рака», а дифференциально экспрессированные гены (ДЭГ) были идентифицированы с помощью различных алгоритмов кластеризации и классификации. Результаты этого анализа позволили предположить, что гены BDKRB1, NMUR2, PMCH и SAA1 могут быть потенциальными прогностическими биомаркерами и новыми терапевтическими мишенями для пПКК.

Хромофобная ПКК

Хромофобная почечно-клеточная карцинома (хПКК) исходит из кортикальныой собирательной трубочки и встречается в 3-5% случаев. Прогноз при хПКК значительно лучше, чем при светлоклеточной и папиллярной ПКК, а 5-летняя выживаемость составляет более 90%.

Ядра часто имеют характерный неравномерный морщинистый (изюмоподобный) вид, часто встречается двуядерность. Морфология клеток очень разнообразна, что может сбить с толку неопытного наблюдателя и привести к негативным заключениям.

Несмотря на то, что были предложены системы классификации хПКК, ни одна из них в настоящее время не получила широкого признания и не включена в клинические рекомендации. Классификация WHO/ISUP также не была валидирована применительно к хПКК. В настоящее время предлагаются двух-, трех- и четырехступенчатые системы классификации, наиболее ярким примером которых является трехступенчатая классификация Панера. Однако дополнительная прогностическая ценность после учета стадии TNM и саркоматоидной дифференцировки отсутствует.

Согласно классификации ВОЗ, хПКК подразделяется на два подтипа: классический и эозинофильный. Для классической хПКК характерны крупные клетки с ретикулярной цитоплазмой и выраженными клеточными мембранами (бледные клетки). Охаши и другие авторы изучили три выборки пациентов: 42 из отделения патологии и молекулярной патологии Университетской больницы Цюриха, 199 из различных институтов и медицинских клиник Японии и 66 из «Атласа генома рака». Разницы в выживаемости между эозинофильным и классическим типами не было ни в одной из выборок пациентов. Для определения корреляции между генотипом и фенотипом был проведен геномный анализ с помощью набора Affymetrix OncoScan CNV Assay (Affymetrix/Thermo Fisher Scientific, Waltham, MA, USA) в 33 хПКК. В объединенных выборках швейцарских пациентов и пациентов из «Атласа генома рака» потери хромосом 1, 2, 6, 10, 13 и 17 достоверно чаще встречались при классическом варианте (p < 0,05 для каждой), что свидетельствует о том, что классическая хПКК характеризуется более высокой хромосомной нестабильностью. Это молекулярное различие позволяет выделить два варианта хПКК.

Трудность диагностики почечно-клеточной карциномы (ПКК) заключается в дифференциации ПКК от доброкачественной онкоцитомы почки. Эти типы опухолей гистологически и морфологически схожи, но требуют разного клинического лечения. В литературе имеется большое количество статей, в которых машинное обучение использовалось для дифференциации онкоцитомы от хПКК с помощью компьютерной томографии и других рентгенологических методов. В одной из публикаций Кевин Бреннан и др. проанализировали метилирование ДНК в свежезамороженных образцах онкоцитомы и хПКК и использовали машинное обучение для выявления сигнатур дифференциально метилированных цитозин-фосфат-гуаниновых (CpG) сайтов, которые достоверно отличали онкоцитому от ПКК. Удивительно, но онкоцитома характеризовалась большим количеством аномального метилирования, чем хПКК. Всего было выявлено 79 CpG с большими различиями в метилировании между онкоцитомой и хПКК. Диагностическая модель позволила отличить онкоцитому от хПКК при 10-кратной перекрестной валидации (AUC = 0,96 (95% ДИ, 0,88-1,00)). Профиль CpG также позволяет дифференцировать онкоцитому от других подтипов ПКК, а также от нормальной ткани, что делает его потенциальным диагностическим биомаркером для онкоцитомы.

Заключение

Появление цифровой патологии особенно с интеграцией искусственного интеллекта стало катализатором трансформационных изменений в нефропатологии. В данном обзоре обобщены последние исследования, изучающие возможности использования ИИ в диагностике и прогнозировании рака почки.

Поскольку мир патологии готов к трансформационным изменениям нельзя недооценивать потенциальные преимущества цифровой патологии, особенно в сочетании с ИИ. Достижения в этой области могут проложить путь к более быстрому принятию решений, повышению точности диагностики, эффективности рабочих процессов и более точному прогнозированию развития заболевания.

Цифровая патология, изменяя стандарты диагностики и роль патологоанатомов, обещает беспрецедентную эффективность в нефропатологии. Например, все большее внимание уделяется использованию ИИ для повышения точности диагностики: от детального клеточного анализа до углубленной оценки микроокружения опухоли и определения прогностических гистологических биомаркеров – и все это в рамках существующих клинических протоколов.

Однако на пути к беспрепятственной интеграции технологий ИИ в рабочие процессы патологоанатомов не обойтись без трудностей. Прежде всего, это стоимость: установка для цифровой патологии, включающая гистосканер, сервер изображений и необходимое программное обеспечение, стоит около 500 тыс. долл. Большинство имеющихся технических решений еще не прошли сертификацию как медицинские изделия. Кроме того, отсутствует валидация различных сканеров и наборов данных. Различия в методах окрашивания и способах сканирования могут приводить к появлению артефактов, что требует принятия мер по контролю качества и корректировки дефектов изображения, таких как сжатие. Для прогнозирования рака почки в настоящее время происходит переход от традиционной ядерной градации к более точному анализу плотности клеток, хотя прогностическая эффективность такого подхода остается неизученной.

В обозримом будущем ожидается, что внедрение ИИ в патологии будет опережать развитие многих других областей. Во многом это объясняется тем, что специалисты могут быстро оценить полезность инструментас ИИ. В ближайшие годы решения на базе ИИ позволят устранить проблемные места в работе патологоанатомов и впоследствии внедрить инновации в области мультимодальных анализов, включающих морфологию, компьютерную томографию, генетику, а также биофотонику.

В то же время существует острая необходимость в проведении тщательных исследований программ искусственного интеллекта, чтобы подкрепить эмпирические выводы. В настоящее время несколько центров располагают обширными базами данных, проводятся рандомизированные исследования с использованием различных моделей сканеров, методов окрашивания и протоколов иммуногистохимии. Эти ресурсы могут способствовать проведению клинических испытаний, в которых традиционные методы диагностики будут сравниваться с новаторскими методиками, прокладывая путь к научно обоснованному, дополненному ИИ будущему в патологии.

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  • 30.07.26 00:04 Ahmed

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  • 04.08.26 11:05 Kisnoles

    Excellent analysis, thank you. I was particularly struck by how rigidly the skill sets the order: data processing and form come first, with color coming last. This really cures the habit of "first a pretty palette, then we'll figure it out." A palette validator using OKLCH + color blindness + WCAG is something most chart generators lack. And regarding the boundaries of competence, it's very clear. Where there's a self-checking loop (color), you delegate freely. Where there's a heuristic (form, data interpretation), you remain the final filter. This is a universal principle, not just for /dataviz. By the way, when you look at trading dashboards (including those of decent platforms like ExpertOption), it's immediately clear who thought about readability and who just threw in rainbow lines. Tools like this skill could greatly improve the quality of analytics. Thanks again for the detailed analysis – saved.

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  • 23.08.26 20:02 leslieyee

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  • 30.08.26 15:37 [email protected]

    Discovering I had been defrauded, I searched online for services claiming to recover stolen ETH. I contacted several companies, but none succeeded. Although some claimed they could trace assets or recover funds, I could not verify their success or recover my money. I later found SYLVESTER BRYANT Recovery through Google. After contacting him, he recovered 450,000,00. He can be reached at [email protected] or WhatsApp at +1 512 577 7957.

  • 01.09.26 11:16 lisawerth897

    My Experience With Cryptocurrency — CAPITAL CRYPTO RECOVER I lost over $82,000 in Bitcoin after falling victim to a fraudulent online investment scheme. After realizing I had been scammed, I spent considerable time researching possible ways to recover my funds. During my research, I came across CAPITAL CRYPTO RECOVER and decided to contact them after reading their reported success record and encouraging client positive reviews and testimonials. Their team guided me through the recovery process, and I was grateful to successfully recover my lost cryptocurrency. The experience was challenging, but I appreciated the assistance and support I received throughout the process. I’m sharing my experience in the hope that it may encourage other victims to carefully research their options and verify any recovery service before proceeding. I will forever be thankful to you CAPITAL CRYPTO RECOVER 📧 [email protected] 🌐 Website: recovercapital.wixsite.com/capital-crypto-rec-1 📧 [email protected] 📞 Call/WhatsApp: +1 (336) 390-6684

  • 01.09.26 11:16 lisawerth897

    My Experience With Cryptocurrency — CAPITAL CRYPTO RECOVER I lost over $82,000 in Bitcoin after falling victim to a fraudulent online investment scheme. After realizing I had been scammed, I spent considerable time researching possible ways to recover my funds. During my research, I came across CAPITAL CRYPTO RECOVER and decided to contact them after reading their reported success record and encouraging client positive reviews and testimonials. Their team guided me through the recovery process, and I was grateful to successfully recover my lost cryptocurrency. The experience was challenging, but I appreciated the assistance and support I received throughout the process. I’m sharing my experience in the hope that it may encourage other victims to carefully research their options and verify any recovery service before proceeding. I will forever be thankful to you CAPITAL CRYPTO RECOVER 📧 [email protected] 🌐 Website: recovercapital.wixsite.com/capital-crypto-rec-1 📧 [email protected] 📞 Call/WhatsApp: +1 (336) 390-6684

  • 01.09.26 17:34 Garry42

    Really crazy world. These fraudsters go at any length to steal your hard earned funds. I have been a victim of a bitcoin scam about 7 months back. A Con artist gained access to my cashapp account through a phishing scam. They stole $409,000. I was really devastated. I did everything to get back my funds by contacting the FBI but they claimed there was nothing they could do. A friend told me about a recovery expert. He helps fight against various phishing and investment scams and they were able to help trace and recover my funds even though it took over 2 days. you can reach out to him through recoverydarek@gmail. com . I can guarantee his services are still active.

  • 01.09.26 17:34 Garry42

    Really crazy world. These fraudsters go at any length to steal your hard earned funds. I have been a victim of a bitcoin scam about 7 months back. A Con artist gained access to my cashapp account through a phishing scam. They stole $409,000. I was really devastated. I did everything to get back my funds by contacting the FBI but they claimed there was nothing they could do. A friend told me about a recovery expert. He helps fight against various phishing and investment scams and they were able to help trace and recover my funds even though it took over 2 days. you can reach out to him through recoverydarek@gmail. com . I can guarantee his services are still active.

  • 02.09.26 03:43 kimberlyhebertt6877

    I invested in bitcoin trading After losing $78.4 USDT) linked to a romance fraud scam worth of cryptocurrency through an online investment platform and later discovered it was a scam. After extensive research for recovery options, I contacted CAPITAL CRYPTO RECOVER based on positive client reviews and recommendations. Their professional security team guided me through the recovery process using advanced technology, and I was able to recover my lost cryptocurrency successfully. I am truly grateful for their support and assistance during such a difficult experience. I will advise you to contact CAPITAL CRYPTO RECOVER helped me recover my funds. For anyone facing similar issues, Website: https://recovercapital.wixsite.com/capital-crypto-rec-1 Email: [email protected] Telegram: @Capitalcryptorecover Contact: [email protected] WhatsApp/Text Number: +1 (336) 390-6684

  • 02.09.26 03:43 kimberlyhebertt6877

    I invested in bitcoin trading After losing $78.4 USDT) linked to a romance fraud scam worth of cryptocurrency through an online investment platform and later discovered it was a scam. After extensive research for recovery options, I contacted CAPITAL CRYPTO RECOVER based on positive client reviews and recommendations. Their professional security team guided me through the recovery process using advanced technology, and I was able to recover my lost cryptocurrency successfully. I am truly grateful for their support and assistance during such a difficult experience. I will advise you to contact CAPITAL CRYPTO RECOVER helped me recover my funds. For anyone facing similar issues, Website: https://recovercapital.wixsite.com/capital-crypto-rec-1 Email: [email protected] Telegram: @Capitalcryptorecover Contact: [email protected] WhatsApp/Text Number: +1 (336) 390-6684

  • 04.09.26 21:51 Kovengray

    Recovering your lost investment funds as the case might be, is not what you can do alone, you’d require the service of a trained recovery specialist. A recovery specialist is a person or a group of people who are well equipped to work around the brokerage network. They have vast knowledge about the whole network and have the right software and private keys to follow any transaction. I was ripped off trading online to an investment broker, good thing I got every penny back through the help of Gavin ray he’s a genius Contact : Gavinray78 at gmail com or WhatsApp +1 352 322 2096 It is also important to be patient and really calm during the process.

  • 05.09.26 21:38 [email protected]

    I invested 45,000  Euro, and later aggreviated to 198,000 Euro.  I requested  to place ‎Withdrawal of my funds to be paid to my Bank account. But nothing happened I was subjected to pay more fee until I can get my funds on my account, i got in touch with Theodore ryan here on this platform who had helped a lot of people, I followed all instructions and he legally got back my withheld funds, I got threatened by the company that if I don’t pay they will get my account frozen, all thanks to Theodore ryan and I highly recommend him to anyone dealing with an unregulated broker company… contact him on his Gmail - theodoreryan318@  gmail .  com

  • 09.09.26 21:31 lisawerth897

    My Experience With Cryptocurrency — CAPITAL CRYPTO RECOVER I lost over $82,000 in Bitcoin after falling victim to a fraudulent online investment scheme. After realizing I had been scammed, I spent considerable time researching possible ways to recover my funds. During my research, I came across CAPITAL CRYPTO RECOVER and decided to contact them after reading their reported success record and encouraging client positive reviews and testimonials. Their team guided me through the recovery process, and I was grateful to successfully recover my lost cryptocurrency. The experience was challenging, but I appreciated the assistance and support I received throughout the process. I’m sharing my experience in the hope that it may encourage other victims to carefully research their options and verify any recovery service before proceeding. I will forever be thankful to you CAPITAL CRYPTO RECOVER 📧 [email protected] 🌐 Website: recovercapital.wixsite.com/capital-crypto-rec-1 📧 [email protected] 📞 Call/WhatsApp: +1 (336) 390-6684

  • 09.09.26 21:31 lisawerth897

    My Experience With Cryptocurrency — CAPITAL CRYPTO RECOVER I lost over $82,000 in Bitcoin after falling victim to a fraudulent online investment scheme. After realizing I had been scammed, I spent considerable time researching possible ways to recover my funds. During my research, I came across CAPITAL CRYPTO RECOVER and decided to contact them after reading their reported success record and encouraging client positive reviews and testimonials. Their team guided me through the recovery process, and I was grateful to successfully recover my lost cryptocurrency. The experience was challenging, but I appreciated the assistance and support I received throughout the process. I’m sharing my experience in the hope that it may encourage other victims to carefully research their options and verify any recovery service before proceeding. I will forever be thankful to you CAPITAL CRYPTO RECOVER 📧 [email protected] 🌐 Website: recovercapital.wixsite.com/capital-crypto-rec-1 📧 [email protected] 📞 Call/WhatsApp: +1 (336) 390-6684

  • 09.09.26 23:22 Fraddy Pual

    Hearing that these individuals are focusing on other people makes me very sad. I had a similar situation with them and lost a lot of money, but after learning about (Cruxcipherteam @ proton DoT me), whataqq:+168160-15021, telegram: @Cruxcipherteam I was able to get my money back. It's critical that we all be watchful and keep reporting these occurrences.

  • 11.09.26 03:23 kimberlyhebertt6877

    I invested in bitcoin trading After losing $78.4 USDT) linked to a romance fraud scam worth of cryptocurrency through an online investment platform and later discovered it was a scam. After extensive research for recovery options, I contacted CAPITAL CRYPTO RECOVER based on positive client reviews and recommendations. Their professional security team guided me through the recovery process using advanced technology, and I was able to recover my lost cryptocurrency successfully. I am truly grateful for their support and assistance during such a difficult experience. I will advise you to contact CAPITAL CRYPTO RECOVER helped me recover my funds. For anyone facing similar issues, Website: https://recovercapital.wixsite.com/capital-crypto-rec-1 Email: [email protected] Telegram: @Capitalcryptorecover Contact: [email protected] WhatsApp/Text Number: +1 (336) 390-6684

  • 11.09.26 03:23 kimberlyhebertt6877

    I invested in bitcoin trading After losing $78.4 USDT) linked to a romance fraud scam worth of cryptocurrency through an online investment platform and later discovered it was a scam. After extensive research for recovery options, I contacted CAPITAL CRYPTO RECOVER based on positive client reviews and recommendations. Their professional security team guided me through the recovery process using advanced technology, and I was able to recover my lost cryptocurrency successfully. I am truly grateful for their support and assistance during such a difficult experience. I will advise you to contact CAPITAL CRYPTO RECOVER helped me recover my funds. For anyone facing similar issues, Website: https://recovercapital.wixsite.com/capital-crypto-rec-1 Email: [email protected] Telegram: @Capitalcryptorecover Contact: [email protected] WhatsApp/Text Number: +1 (336) 390-6684

  • 15.09.26 03:35 elioduncan

    I fell victim to a freelance web development contract scam that ultimately cost me CAD 4,000. It all started when I came across a job posting on Indeed Canada, a popular online job portal. The position seemed perfect: a freelance web developer role for an established company looking for someone to design and build a fully functional e-commerce website. The job promised a high payment of CAD 20,000 upon successful completion, which sounded like a great opportunity for me to gain experience and earn decent pay.The employer, who introduced himself as a project manager from a "well-known" tech company, was very persuasive and professional in our initial communication. He explained that the project involved developing a user-friendly, responsive online store for their client and that they had a strict timeline to meet. He assured me that the payment would be made promptly after completing the tasks. However, before starting the work, he told me that I would need to pay an upfront fee of CAD 4,000 to cover certain software tools and licensing fees required for the project. This was supposedly a part of their company policy for freelance contractors, ensuring access to their premium resources. The idea of working on a professional project, coupled with the promise of a substantial payout, convinced me to pay the upfront fee.As soon as I made the payment, the project manager became increasingly difficult to reach. He initially responded to my emails and provided some vague instructions on what the project would entail, but as time went on, communication slowed to a complete halt. I never received the required tools or any proper project details. My emails went unanswered, and any attempts to contact the company were met with silence. After waiting for weeks, I realized that I had been scammed.Desperate to recover my money, I turned to TechY Force Cyber Retrieval, a service that specializes in helping victims of online scams. They helped me track the payment and took legal steps to pursue the fraudsters. Through their guidance, I was able to recover the full CAD 4,000. TechY Force Cyber Retrieval worked with my bank to reverse the transaction and liaised with the authorities to trace the scammer's details.This was a hard lesson, and I now know to be highly cautious about online job offers that require upfront payments. It is crucial to research companies thoroughly and avoid any job that seems too good to be true, especially when it involves paying money upfront. WhatsApp https://wa.link/2x6ktp Mail. [email protected]

  • 15.09.26 15:45 lydiassmith567

    HIRE A HACKER YOUR STOLEN CRYPTO RECOVERY / BTC / USDT / ETH WITH THE HELP OF CAPITAL CRYPTO RECOVER. I want to share my experience publicly regarding cryptocurrency wallet recovery, I highly recommend you to contact CAPITAL CRYPTO RECOVER, a professional private investigator in the Bitcoin world. They have a certified expert security team specializing in Bitcoin Recovery Services and have helped many people worldwide recover their lost funds. My wife and I were defrauded by an online manipulator posing as an experienced crypto investment professional. We lost $9.2 Million Stolen BTC in cryptocurrency and were left feeling homeless. After spending hours searching for a reliable crypto recovery service, I discovered CAPITAL CRYPTO RECOVER online. By patiently explaining my situation to their team, I was able to recover all my funds. Remarkably, my money was returned to my wallet in less than 24 hours. I am extremely grateful to CAPITAL CRYPTO RECOVER for their excellent assistance—they truly were a godsend in my difficult situation. If you have fallen victim to a cryptocurrency scam, you can reach CAPITAL CRYPTO RECOVER through the following channels Email: [email protected] OR Call/WhatsApp: +1 (336) 390-6684 Contact: [email protected] Website: https://recovercapital.wixsite.com/capital-crypto-rec-1

  • 15.09.26 15:45 lydiassmith567

    HIRE A HACKER YOUR STOLEN CRYPTO RECOVERY / BTC / USDT / ETH WITH THE HELP OF CAPITAL CRYPTO RECOVER. I want to share my experience publicly regarding cryptocurrency wallet recovery, I highly recommend you to contact CAPITAL CRYPTO RECOVER, a professional private investigator in the Bitcoin world. They have a certified expert security team specializing in Bitcoin Recovery Services and have helped many people worldwide recover their lost funds. My wife and I were defrauded by an online manipulator posing as an experienced crypto investment professional. We lost $9.2 Million Stolen BTC in cryptocurrency and were left feeling homeless. After spending hours searching for a reliable crypto recovery service, I discovered CAPITAL CRYPTO RECOVER online. By patiently explaining my situation to their team, I was able to recover all my funds. Remarkably, my money was returned to my wallet in less than 24 hours. I am extremely grateful to CAPITAL CRYPTO RECOVER for their excellent assistance—they truly were a godsend in my difficult situation. If you have fallen victim to a cryptocurrency scam, you can reach CAPITAL CRYPTO RECOVER through the following channels Email: [email protected] OR Call/WhatsApp: +1 (336) 390-6684 Contact: [email protected] Website: https://recovercapital.wixsite.com/capital-crypto-rec-1

  • 05.10.26 21:26 [email protected]

    I Invested 45,000  Euro, and later aggreviated to 198,000 Euro.  I requested  to place Withdrawal of my funds to be paid to my Bank account. But nothing happened I was subjected to pay more fee until I can get my funds on my account, i got in touch with Theodore ryan here on this platform who had helped a lot of people, I followed all instructions and he legally got back my withheld funds, I got threatened by the company that if I don’t pay they will get my account frozen, all thanks to Theodore ryan and I highly recommend him to anyone dealing with an unregulated broker company… contact him on his Gmail - theodoreryan318@  gmail .  com

  • 06.10.26 06:13 melissathomason573

    Professional Crypto Recovery Testimonial After losing a significant amount of cryptocurrency through a scam on Twitter, I was unsure whether my Bitcoin funds could ever be recovered. The experience was extremely stressful, particularly because I encountered several individuals and services claiming they could help recover my assets, only to discover that some were fraudulent themselves. A friend eventually referred me to CAPITAL CRYPTO RECOVER. Their team handled my case professionally, discreetly, and efficiently. With their assistance, I successfully recovered approximately $130,000 worth of USDT in just over a week. My experience taught me the importance of being extremely cautious when seeking cryptocurrency recovery services, as scammers often target victims a second time. I am grateful to CAPITAL CRYPTO RECOVER for the assistance I received and wanted to share my experience with others who may be facing a similar situation. If you’ve been compromised, don’t lose hope—and be careful of fraudsters posing as saviors. CAPITAL CRYPTO RECOVER are real professionals in crypto recovery. I am a living proof of their effectiveness, you can reach them through Phone (Call/WhatsApp): +1 (336) 390-6684 Email: [email protected] Alternate Email: [email protected] Website: https://recovercapital.wixsite.com/capital-crypto-rec-1

  • 06.10.26 06:13 melissathomason573

    Professional Crypto Recovery Testimonial After losing a significant amount of cryptocurrency through a scam on Twitter, I was unsure whether my Bitcoin funds could ever be recovered. The experience was extremely stressful, particularly because I encountered several individuals and services claiming they could help recover my assets, only to discover that some were fraudulent themselves. A friend eventually referred me to CAPITAL CRYPTO RECOVER. Their team handled my case professionally, discreetly, and efficiently. With their assistance, I successfully recovered approximately $130,000 worth of USDT in just over a week. My experience taught me the importance of being extremely cautious when seeking cryptocurrency recovery services, as scammers often target victims a second time. I am grateful to CAPITAL CRYPTO RECOVER for the assistance I received and wanted to share my experience with others who may be facing a similar situation. If you’ve been compromised, don’t lose hope—and be careful of fraudsters posing as saviors. CAPITAL CRYPTO RECOVER are real professionals in crypto recovery. I am a living proof of their effectiveness, you can reach them through Phone (Call/WhatsApp): +1 (336) 390-6684 Email: [email protected] Alternate Email: [email protected] Website: https://recovercapital.wixsite.com/capital-crypto-rec-1

  • 06.10.26 17:44 Darrell1717

    I fell victim of a scam I invested to total of 5thousand into. I know it could be risky but after I trusted this man I was dating online he lured me into investing with him. I know hard I worked of my money so I wanted every way possible to get it back. I really appreciate Blockrecoveryexpert for successfully recovered my funds form this scammer. This is all I can say. You can reachout if you ever need help contact blockrecoveryexpert (at) gmail (dot)com

  • 11.10.26 03:04 Patricia014

    Most recovery companies will take your money again. I personally think they’re the same set of people running all of them. It’s a sad, unending cycle, and so many people fall for cloned websites. The only recovery agent I know is Agent Rottgen Raphael. I’ve visited their physical company address, and they’ll tell you if they can handle your case instead of taking upfront payment when they know they can’t help. I highly appreciate their support in recovering my money from the scammers’ wallet within 24 hours. RottgenRaphael@Gmail. com

  • 12.10.26 19:34 lydiassmith567

    HIRE A HACKER YOUR STOLEN CRYPTO RECOVERY / BTC / USDT / ETH WITH THE HELP OF CAPITAL CRYPTO RECOVER. I want to share my experience publicly regarding cryptocurrency wallet recovery, I highly recommend you to contact CAPITAL CRYPTO RECOVER, a professional private investigator in the Bitcoin world. They have a certified expert security team specializing in Bitcoin Recovery Services and have helped many people worldwide recover their lost funds. My wife and I were defrauded by an online manipulator posing as an experienced crypto investment professional. We lost $9.2 Million Stolen BTC in cryptocurrency and were left feeling homeless. After spending hours searching for a reliable crypto recovery service, I discovered CAPITAL CRYPTO RECOVER online. By patiently explaining my situation to their team, I was able to recover all my funds. Remarkably, my money was returned to my wallet in less than 24 hours. I am extremely grateful to CAPITAL CRYPTO RECOVER for their excellent assistance—they truly were a godsend in my difficult situation. If you have fallen victim to a cryptocurrency scam, you can reach CAPITAL CRYPTO RECOVER through the following channels Email: [email protected] OR Call/WhatsApp: +1 (336) 390-6684 Contact: [email protected] Website: https://recovercapital.wixsite.com/capital-crypto-rec-1

  • 12.10.26 19:34 lydiassmith567

    HIRE A HACKER YOUR STOLEN CRYPTO RECOVERY / BTC / USDT / ETH WITH THE HELP OF CAPITAL CRYPTO RECOVER. I want to share my experience publicly regarding cryptocurrency wallet recovery, I highly recommend you to contact CAPITAL CRYPTO RECOVER, a professional private investigator in the Bitcoin world. They have a certified expert security team specializing in Bitcoin Recovery Services and have helped many people worldwide recover their lost funds. My wife and I were defrauded by an online manipulator posing as an experienced crypto investment professional. We lost $9.2 Million Stolen BTC in cryptocurrency and were left feeling homeless. After spending hours searching for a reliable crypto recovery service, I discovered CAPITAL CRYPTO RECOVER online. By patiently explaining my situation to their team, I was able to recover all my funds. Remarkably, my money was returned to my wallet in less than 24 hours. I am extremely grateful to CAPITAL CRYPTO RECOVER for their excellent assistance—they truly were a godsend in my difficult situation. If you have fallen victim to a cryptocurrency scam, you can reach CAPITAL CRYPTO RECOVER through the following channels Email: [email protected] OR Call/WhatsApp: +1 (336) 390-6684 Contact: [email protected] Website: https://recovercapital.wixsite.com/capital-crypto-rec-1

  • 13.10.26 14:14 lisalisa22

    Legitimate Cryptocurrency Recovery Services: Consult ZEUS CRYPTO RECOVERY SERVICES Zeus Crypto Recovery Services supports individuals exploring options after cryptocurrency losses from fraud, unauthorised transfers, or wallet access issues. Services may include blockchain analysis, wallet tracing, and evidence gathering for investigations. Each case is reviewed. Zeus Crypto Recovery Services is a trusted company with the highest success rate among cryptocurrency recovery services in 2025/2026 and is highly recommended if you have been scammed. ZEUS CRYPTO RECOVERY SERVICES handles case such as Scammed USDT Lost BTC, Coinbase Wallet Forgotten password, ETH and coins, etc. Anything that has to do with cryptocurrency or lost digital assets, ZEUS can help you Do you Need Help? Website https://zeusrecoveryservices.com Mailbox [email protected] WhatsApp number +447798816938 Telegram https://t.me/Zeuscryptorecoveryservices

  • 13.10.26 14:14 lisalisa22

    Legitimate Cryptocurrency Recovery Services: Consult ZEUS CRYPTO RECOVERY SERVICES Zeus Crypto Recovery Services supports individuals exploring options after cryptocurrency losses from fraud, unauthorised transfers, or wallet access issues. Services may include blockchain analysis, wallet tracing, and evidence gathering for investigations. Each case is reviewed. Zeus Crypto Recovery Services is a trusted company with the highest success rate among cryptocurrency recovery services in 2025/2026 and is highly recommended if you have been scammed. ZEUS CRYPTO RECOVERY SERVICES handles case such as Scammed USDT Lost BTC, Coinbase Wallet Forgotten password, ETH and coins, etc. Anything that has to do with cryptocurrency or lost digital assets, ZEUS can help you Do you Need Help? Website https://zeusrecoveryservices.com Mailbox [email protected] WhatsApp number +447798816938 Telegram https://t.me/Zeuscryptorecoveryservices

  • 17.10.26 12:58 melissathomason573

    Professional Crypto Recovery Testimonial After losing a significant amount of cryptocurrency through a scam on Twitter, I was unsure whether my Bitcoin funds could ever be recovered. The experience was extremely stressful, particularly because I encountered several individuals and services claiming they could help recover my assets, only to discover that some were fraudulent themselves. A friend eventually referred me to CAPITAL CRYPTO RECOVER. Their team handled my case professionally, discreetly, and efficiently. With their assistance, I successfully recovered approximately $130,000 worth of USDT in just over a week. My experience taught me the importance of being extremely cautious when seeking cryptocurrency recovery services, as scammers often target victims a second time. I am grateful to CAPITAL CRYPTO RECOVER for the assistance I received and wanted to share my experience with others who may be facing a similar situation. If you’ve been compromised, don’t lose hope—and be careful of fraudsters posing as saviors. CAPITAL CRYPTO RECOVER are real professionals in crypto recovery. I am a living proof of their effectiveness, you can reach them through Phone (Call/WhatsApp): +1 (336) 390-6684 Email: [email protected] Alternate Email: [email protected] Website: https://recovercapital.wixsite.com/capital-crypto-rec-1

  • 17.10.26 12:58 melissathomason573

    Professional Crypto Recovery Testimonial After losing a significant amount of cryptocurrency through a scam on Twitter, I was unsure whether my Bitcoin funds could ever be recovered. The experience was extremely stressful, particularly because I encountered several individuals and services claiming they could help recover my assets, only to discover that some were fraudulent themselves. A friend eventually referred me to CAPITAL CRYPTO RECOVER. Their team handled my case professionally, discreetly, and efficiently. With their assistance, I successfully recovered approximately $130,000 worth of USDT in just over a week. My experience taught me the importance of being extremely cautious when seeking cryptocurrency recovery services, as scammers often target victims a second time. I am grateful to CAPITAL CRYPTO RECOVER for the assistance I received and wanted to share my experience with others who may be facing a similar situation. If you’ve been compromised, don’t lose hope—and be careful of fraudsters posing as saviors. CAPITAL CRYPTO RECOVER are real professionals in crypto recovery. I am a living proof of their effectiveness, you can reach them through Phone (Call/WhatsApp): +1 (336) 390-6684 Email: [email protected] Alternate Email: [email protected] Website: https://recovercapital.wixsite.com/capital-crypto-rec-1

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