Behavior analysis in practice · 2025
Are Keynote and Invited Speakers at State Behavior Analytic Conferences Experts on Their Presentation Topics?
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Laaksonen R, Janatuinen T, Vesalainen R, Lehtimäki T, Elovaara I, Jaakkola O, Jokela H, Laakso J, Nuutila P, Punnonen K, Raitakari O, Saikku P, Salminen K, Knuuti J
Аннотация
UNLABELLED: Prostate cancer poses a significant threat to men's health worldwide. Docetaxel (DTX) remains a cornerstone chemotherapeutic agent for PC, yet the emergence of docetaxel resistance has critically compromised clinical outcomes. Elucidating the molecular mechanisms underlying docetaxel resistance and identifying novel therapeutic targets are therefore imperative. This study integrated transcriptomic profiles and clinical data from the The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) and Gene Expression Omnibus (GEO) databases to identify PCDHGB2 as a pivotal gene associated with docetaxel resistance. Bioinformatics analyses were systematically conducted to evaluate correlations between PCDHGB2 expression, tumor microenvironment heterogeneity, clinicopathological characteristics, and patient prognosis. Experimental validation included quantitative real-time PCR (RT-qPCR) and immunofluorescence for expression profiling, Cell Counting Kit-8 (CCK-8) assays for cellular viability assessment, alongside co-immunoprecipitation and molecular docking to characterize protein interactions. Our findings demonstrate that PCDHGB2 serves as a central mediator of docetaxel resistance in PC, exhibiting significant associations with tumor microenvironment heterogeneity. Spatial analysis revealed differential PCDHGB2 distribution across prostate carcinoma cell subtypes, correlating with tumor invasiveness. Mechanistically, PCDHGB2 directly binds to testicular receptor 4 (TR4), stabilizing its expression and subsequently activating the hypoxia-inducible factor 1-alpha (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling axis to drive chemoresistance. To our knowledge, this study provides an initial comprehensive analysis of PCDHGB2's functional role in prostate cancer, uncovers a poorly recognized epigenetic mechanism of docetaxel resistance, and suggests a theoretical framework for improving prognostic strategies in prostate cancer patients.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-026-01051-2.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-026-01051-2.