Молекулярные детерминанты рецидива уротелиальной опухоли человека

Background. Urothelial carcinoma (UTC) is an aggressive disease with a known propensity for frequent recurrence. It is difficult to predict the velocity of the development of UTC recur using modern means of clinical diagnostics. Therefore, the development of the capabilities of histo-morphological study of tumor tissues is of particular relevance.Materials and methods. The materials of publications (PubMed, CrossRef) for 1990-2021, devoted to the choice of biomarkers for the diagnosis of UTC, the analysis of molecular pathways, progression and metastasis, were studied. The search was carried out for the key phrases "urothelial carcinoma", "recurrent UTK", "stem cells", "biomarkers of bladder cancer", "genetic changes in urothelium", "circulating tumor DNA".Results. Cancer stem cells serve as a source of UTC recurrence after removal from the primary focus, localizing in any areas of the urothelium, as well as outside the main tumor focus and are characterized by a common genotype, but different phenotypic manifestations. To predict the recurrence of the tumour is advisable to use gene expression signatures, since the subtypes of UTC are characterized by clear gene expression profiles. A larger sample and independent dataset is needed to confirm the clinical significance of the findings. Combined biomarkers predict UTC behavior, and FGFR3 and TP53 mutations can be components for a panel for predicting UTC recurrence. The use of the liquid biopsy method with the determination of the level of circulating tumor DNA is a promising diagnostic method that needs to evaluate the results of an initiated randomized trial.Conclusion. The accumulation of knowledge base about the molecular patterns of UTC will help bridge the gap between the results of molecular genetic and clinical diagnostics. Molecular changes in the transitional cell UTC demonstrates a high potential for determining the timing of tumor recurrence, assessing disease-free survival of patients and for planning the resource base of the healthcare system.Введение. Уротелиальная карцинома (УТК) - агрессивное заболевание со склонностью к частому рецидивированию. Прогноз развития рецидивов УТК с помощью современных средств клинической диагностики затруднен, поэтому особую актуальность приобретает развитие возможностей патоморфологического исследования опухолевых тканей.Материалы и методы. Изучены материалы публикаций (PubMed, CrossRef) за 1990-2021 гг., посвященных вопросам выбора биомаркеров для диагностики УТК, анализу молекулярных путей прогрессирования и метастазирования. Поиск проводили по ключевым фразам «уротелиальная карцинома», «рецидив уротелиальной карциномы», «стволовые клетки», «биомаркеры рака мочевого пузыря», «генетические изменения уротелия», «циркулирующая опухолевая ДНК».Результаты. Раковые стволовые клетки служат источником рецидива УТК после удаления первичного очага, локализуясь в любых участках уротелия, а также вне основного очага опухоли, и характеризуются общим генотипом, но различными фенотипическими проявлениями. Для прогноза рецидива УТК целесообразно использование экспрессионных сигнатур генов, поскольку для подтипов УТК характерны четкие профили экспрессии генов. Для подтверждения клинического значения полученных данных необходимы большая выборка и независимый набор данных. Комбинированные биомаркеры обеспечивают прогнозирование поведения УТК, а мутации FGFR3 и TP53 могут служить компонентами для панели прогноза рецидива УТК. Использование метода жидкостной биопсии с определением уровня циркулирующей опухолевой ДНК - перспективный метод диагностики, нуждающийся в оценке результатов инициированного рандомизированного исследования.Заключение. Накопление знаний о молекулярных паттернах УТК позволит преодолеть разрыв между результатами молекулярно-генетической и клинической диагностики. Молекулярные изменения УТК демонстрируют высокий потенциал для определения сроков рецидива опухоли, оценки безрецидивной выживаемости пациентов и планирования ресурсной базы системы здравоохранения

Preoperative Typing of Thyroid and Parathyroid Tumors with a Combined Molecular Classifier

In previous studies, we described a method for detecting and typing malignant tumors of the thyroid gland in fine-needle aspiration biopsy samples via analysis of a molecular marker panel (normalized HMGA2 mRNA level; normalized microRNA-146b, -221, and -375 levels; mitochondrial-to-nuclear DNA ratio; and BRAFV600E mutation) in cytological preparations by quantitative PCR. In the present study, we aimed to estimate the specificity of the typing of different thyroid tumors by the proposed method. Fine-needle aspiration cytological preparations from 278 patients were used. The histological diagnosis was known for each sample. The positive and negative predictive values of the method assessed in this study were, respectively, 100% and 98% for papillary thyroid carcinoma (n = 63), 100% and 100% for medullary thyroid carcinoma (n = 19), 43.5% and 98% for follicular carcinoma (n = 15), and 86% and 100% for Hürthle cell carcinoma (n = 6). Thus, we demonstrate that the diagnostic panel, including the analysis of microRNA expression, mRNA expression, the BRAFV600E mutation, and the mitochondrial-to-nuclear DNA ratio, allows the highly accurate identification of papillary thyroid carcinoma, medullary thyroid carcinoma, and Hürthle cell carcinoma but not malignant follicular tumors (positive predictive value was below 50%)

Preoperative Typing of Thyroid and Parathyroid Tumors with a Combined Molecular Classifier

In previous studies, we described a method for detecting and typing malignant tumors of the thyroid gland in fine-needle aspiration biopsy samples via analysis of a molecular marker panel (normalized HMGA2 mRNA level; normalized microRNA-146b, -221, and -375 levels; mitochondrial-to-nuclear DNA ratio; and BRAFV600E mutation) in cytological preparations by quantitative PCR. In the present study, we aimed to estimate the specificity of the typing of different thyroid tumors by the proposed method. Fine-needle aspiration cytological preparations from 278 patients were used. The histological diagnosis was known for each sample. The positive and negative predictive values of the method assessed in this study were, respectively, 100% and 98% for papillary thyroid carcinoma (n = 63), 100% and 100% for medullary thyroid carcinoma (n = 19), 43.5% and 98% for follicular carcinoma (n = 15), and 86% and 100% for Hürthle cell carcinoma (n = 6). Thus, we demonstrate that the diagnostic panel, including the analysis of microRNA expression, mRNA expression, the BRAFV600E mutation, and the mitochondrial-to-nuclear DNA ratio, allows the highly accurate identification of papillary thyroid carcinoma, medullary thyroid carcinoma, and Hürthle cell carcinoma but not malignant follicular tumors (positive predictive value was below 50%)