ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
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
Provisionally accepted
Menglu Li1,2Xinwei Liu1
Yuhui Xue1Yichen Lu2Zhiqiang Chen1
Yuwei Zhang3Weiguo Chen4*Shan-Chao Zhao5*
Ke Wang6*
Ninghan Feng1,2*- 1Jiangnan University Wuxi School of Medicine, Wuxi, China
- 2Wuxi No.2 People's Hospital, Nanjing Medical University, Wuxi, China
- 3Nantong University, Nantong, China
- 4First Affiliated Hospital of Soochow University, Suzhou, China
- 5Southern Medical University, Guangzhou, China
- 6Qingdao University, Qingdao, China
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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. We utilized a multi-step bioinformatics pipeline to analyze molecular differences between NMIBC and MIBC using TCGA and GEO RNA-seq datasets. Differentially expressed genes were identified, and prognostic markers were prioritized through Cox regression and Kaplan–Meier analysis. The regulatory network was explored using protein-protein interaction analysis, and ECM-related activity was quantified through ssGSEA. 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. In 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.
Keywords: COL1A2, Extracellular Matrix, focal adhesion kinase, muscle-invasivebladder cancer, Non-muscle-invasive bladder cancer
Received: 02 Oct 2025; Accepted: 09 Dec 2025.
Copyright: © 2025 Li, Liu, Xue, Lu, Chen, Zhang, Chen, Zhao, Wang and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Weiguo Chen
Shan-Chao Zhao
Ke Wang
Ninghan Feng
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