Background: Cancer-associated fibroblasts (CAFs) are a component of the tumor microenvironment, influencing tumor behavior and progression. This meta-analysis aims to describe the prognostic value of CAF biomarkers in colorectal cancer (CRC).
Methods: A systematic search of the existing literature was performed in Medline and Embase on CAF immunohistochemical (IHC) biomarkers and their association with disease-free survival (DFS) and overall survival (OS). The selection of studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Population, Intervention, Comparator, Outcome criteria. The quality of the included articles was assessed using the Newcastle-Ottawa Scale.
Results: A total of 3,535 records were identified, of which 84 were selected for the qualitative review and 59 (N = 15,396 patients) were included in the final meta-analysis. In general, CAF biomarker expression was associated with poor prognosis, with high heterogeneity among studies. Significant results for DFS were found for cluster of differentiation (CD) 163, matrix metalloproteinase 9 (MMP-9), and tenascin C. The following markers were significantly associated with OS: CD163, MMP-9, periostin, and vimentin.
Conclusion: Several CAF IHC biomarkers, particularly CD163, MMP-9, periostin, and vimentin, significantly associated with prognosis in CRC, could be proposed as surrogates for the phenotypical characterization of the tumor microenvironment.
Keywords: cancer-associated fibroblasts; colorectal cancer; meta-analysis; prognostic biomarkers; tumor microenvironment.
Copyright © 2025 Ilie, Gales, Musina, Rouet, Stefan, Belceanu, Trandafir, Guillaume, Bertaut, Charifi, Cueff, Derangère and Ghiringhelli.