Frontiers in oncology · 2026
Integrative bulk and single-cell transcriptomic analysis reveals COL1A2-driven ECM remodeling and focal adhesion signaling associated with the transition from non-muscle-invasive to muscle-invasive bladder cancer.
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.
Li Menglu, Liu Xinwei, Xue Yuhui, Lu Yichen, Chen Zhiqiang, Zhang Yuwei, Chen Weiguo, Zhao Shan-Chao, Wang Ke, Feng Ninghan
Аннотация
BACKGROUND: Bladder cancer (BCA) shows significant prognostic differences between non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) forms. While NMIBC frequently recurs and can progress to invasive disease, reliable biomarkers to monitor this transition are lacking. Extracellular matrix (ECM) remodeling is a critical factor influencing tumor aggressiveness, yet the key regulators of ECM changes across BCA stages remain unclear. In this study, we investigate the role of COL1A2 in ECM-related tumor biology and its potential as a prognostic biomarker for BCA progression.
METHODS: We utilized a multi-step bioinformatics pipeline, analyzing RNA-seq data from TCGA and GEO datasets to identify molecular differences between NMIBC and MIBC. Prognostic markers were prioritized via differential expression analysis, Cox regression, and Kaplan-Meier survival analysis. The regulatory network was explored using protein-protein interaction analysis, and ECM-related activity was quantified through ssGSEA. Cell-type-specific insights were gained through single-cell RNA-seq analysis, and intercellular communication was deciphered using CellChat. Functional validation was performed through in vitro knockdown experiments in BCA cell lines.
RESULTS: COL1A2 emerged as a key prognostic ECM-related gene associated with MIBC. Single-cell RNA-seq analysis revealed that COL1A2 and ECM components were predominantly enriched in matrix cancer-associated fibroblasts (CAFs), with PTK2 (FAK, focal adhesion kinase) upregulated in epithelial cells undergoing epithelial-mesenchymal transition (EMT). CellChat analysis uncovered a dominant COL1A2-mediated signaling axis from matrix CAFs to EMT epithelial cells via COL1A1/2-SDC1/4 ligand-receptor interactions. Functional assays confirmed that COL1A2 knockdown significantly impaired MIBC cell invasion and migration by suppressing ECM remodeling and EMT.
CONCLUSION: Our results suggest that the COL1A2-ECM-FAK signaling axis plays a critical role in MIBC progression, and COL1A2 could serve as a potential biomarker and therapeutic target for muscle-invasive bladder cancer.
METHODS: We utilized a multi-step bioinformatics pipeline, analyzing RNA-seq data from TCGA and GEO datasets to identify molecular differences between NMIBC and MIBC. Prognostic markers were prioritized via differential expression analysis, Cox regression, and Kaplan-Meier survival analysis. The regulatory network was explored using protein-protein interaction analysis, and ECM-related activity was quantified through ssGSEA. Cell-type-specific insights were gained through single-cell RNA-seq analysis, and intercellular communication was deciphered using CellChat. Functional validation was performed through in vitro knockdown experiments in BCA cell lines.
RESULTS: COL1A2 emerged as a key prognostic ECM-related gene associated with MIBC. Single-cell RNA-seq analysis revealed that COL1A2 and ECM components were predominantly enriched in matrix cancer-associated fibroblasts (CAFs), with PTK2 (FAK, focal adhesion kinase) upregulated in epithelial cells undergoing epithelial-mesenchymal transition (EMT). CellChat analysis uncovered a dominant COL1A2-mediated signaling axis from matrix CAFs to EMT epithelial cells via COL1A1/2-SDC1/4 ligand-receptor interactions. Functional assays confirmed that COL1A2 knockdown significantly impaired MIBC cell invasion and migration by suppressing ECM remodeling and EMT.
CONCLUSION: Our results suggest that the COL1A2-ECM-FAK signaling axis plays a critical role in MIBC progression, and COL1A2 could serve as a potential biomarker and therapeutic target for muscle-invasive bladder cancer.