Cancer-associated fibroblasts and their prognostic role in colorectal cancer: review and meta-analysis

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: = 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.