Identifying the oncogenic roles of FAP in human cancers based on systematic analysis

Background: Fibroblast activation protein-α (FAP) is a specific marker of cancer-associated fibroblasts (CAFs) and plays a crucial role in tumor development. However, the biological processes underlying FAP expression in tumor progression and tumor immunity have not been fully elucidated. Methods: We utilized RNA-seq data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to perform differential analysis of FAP expression in tumor tissues and matched-normal tissues. The relationship between FAP expression and clinical prognosis, DNA methylation, and tumor-infiltrating immune cells in pan-cancer was assessed using R Studio (version 4.2.1). Additionally, we employed gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) to investigate the biological functions and pathways associated with FAP expression. Results: FAP exhibits high expression in most malignancies, albeit to a lesser extent in CESC, KICH, UCEC, SKCM, THCA, and UCS. Furthermore, FAP is either positively or negatively associated with the prognosis of several malignancies. In seven types of cancer, FAP expression is positively correlated with DNA methylation. CIBERSORT analysis revealed an inverse correlation between FAP expression and T cells, B cells, monocytes, and NK cells, while it exhibited a positive correlation with M0, M1, and M2 macrophages. Enrichment analysis further demonstrated that FAP modulates the cell cycle, epithelial-mesenchymal transition (EMT) process, angiogenesis, and immune-related functions and pathways. Conclusion: Our findings indicate a close relationship between FAP expression and tumorigenesis as well as tumor immunity. FAP has the potential to serve as a diagnostic, prognostic, and immunotherapy marker.