Comprehensive analysis of the oncogenic and immunological role of FAP and identification of the ceRNA network in human cancers.

Abstract

Fibroblast activation protein-alpha (FAP) is a transmembrane serine protease involving in tissue remodeling. Previous studies report that FAP is highly expressed in certain tumors and participated in oncogenesis. However, there is still lack of systematic and in-depth analysis of FAP based on clinical big data. Here, we comprehensively map the FAP expression profile, prognostic outcome, genetic alteration, immune infiltration across over 30 types of human cancers through multiple datasets including TCGA, CPTAC, and cBioPortal. We find that FAP is up-regulated in most cancer types, and increased FAP expression is associated with advanced pathological stages or poor prognosis in several cancers. Furthermore, FAP is significantly correlated with the infiltration of cancer-associated fibroblasts, macrophages, myeloid dendritic cells, as well as endothelia cells. Immunosuppressive checkpoint proteins or cytokines expression, microsatellite instability and tumor mutational burden analysis also indicate the regulation role of FAP in tumor progression. Gene enrichment analysis demonstrates that ECM-receptor interaction as well as extracellular matrix and structure process are linked to the potential mechanism of FAP in tumor pathogenesis. The ceRNA network is also constructed and identified the involvement of LINC00707/hsa-miR-30e-5p/FAP, LINC02535/hsa-miR-30e-5p/FAP, LINC02535/hsa-miR-30d-5p/FAP, as well as AC026356.1/hsa-miR-30d-5p/FAP axis in tumor progression. In conclusion, our study offers new insights into the oncogenic and immunological role of FAP from a pan-cancer perspective, providing new clues for developing novel targeted anti-tumor strategies.