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Integrative Bulk and Single-Nucleus Analyses Nominate COL5A2 as a CAF/ECM-Associated Marker Associated with PDAC
Kuan-Ting Lu1, Tsung-Ming Chang2, Chi-Jen Chang3,4
1Department of Neurosurgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111045, Taiwan.
Diagnostics (Basel, Switzerland)
|May 4, 2026
Summary
Collagen type 5 alpha 2 (COL5A2) is a promising biomarker for pancreatic ductal adenocarcinoma (PDAC) progression. Its elevated expression in tumor stroma, particularly in cancer-associated fibroblasts (CAFs), correlates with poorer patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Pancreatic ductal adenocarcinoma (PDAC) features a dense desmoplastic stroma, yet lacks reliable stromal biomarkers for disease progression.
- Identifying such biomarkers is crucial for understanding PDAC development and improving patient outcomes.
Purpose of the Study:
- To identify and validate a novel stromal/extracellular matrix (ECM)-associated biomarker for pancreatic ductal adenocarcinoma.
- To assess the biomarker's association with disease progression and its expression patterns within the tumor microenvironment.
Main Methods:
- Integrated analysis of three GEO bulk transcriptomic PDAC cohorts for differential gene expression and network analysis.
- Validated candidate biomarkers using proteomic data, survival analyses, receiver operating characteristic (ROC) comparisons, and single-nucleus RNA sequencing.
Main Results:
- COL5A2 emerged as a consensus hub gene, showing elevated protein expression in PDAC tissues and correlating with worse overall and disease-free survival.
- COL5A2 demonstrated robust tumor-versus-non-tumor discrimination and outperformed other collagen genes in ROC analyses.
- COL5A2 expression increased with PDAC progression and was significantly associated with ECM and cancer-associated fibroblast (CAF) signatures, predominantly expressed in fibroblast/CAF compartments.
Conclusions:
- COL5A2 is a reproducible stromal/ECM-associated biomarker for pancreatic ductal adenocarcinoma progression.
- Its expression is primarily localized to fibroblasts and CAFs within the tumor microenvironment.
- COL5A2 holds potential for future diagnostic and prognostic applications in PDAC.
