Mixed data analysis detected Endocrine Fibroblast Growth Factors (FGF19, FGF21, and FGF23) as Prognostic and Diagnostic Markers of Colorectal Neoplasia and Carcinoma

Abstract

BackgroundEndocrine fibroblast growth factors (eFGFs) play important roles in various cellular signaling processes such as development and differentiation. These genes were also found to be significantly related to several cancer. However, little is known about the role of eFGFsin colon neoplasia and colon adenocarcinoma (COAD).MethodsWe performed systematically and comprehensively investigated the gene expression, DNA methylation, prognostic significance, genetic alteration, co-expressed genes, protein-protein interaction, small molecules pathway, and drug interactions ofeFGFsbased on the TIMER2.0, GEPIA2, UALCAN, OncoDB, cBioPortal, LinkedOmics, STRING, SMPDB, htfTarget, mirTarBase, circBank and DGIdb databases. Ultimately, the correlations ofeFGFsexpressions between polyp and COAD tissues compared to normal mucosa were validated using qRT-PCR as a cross-sectional part of our study.ResultsThe results indicated thateFGFsare highly expressed in COAD, and abnormal gene expressions may be related to promoter methylation. In this matter, methylation analysis revealed promotor hypermethylation ofFGF19andFGF21. Conversely,FGF23was shown to have a tendency for promotor hypomethylation. Moreover, hypermethylation ofFGF21andFGF23and downregulation ofFGF23were found to be detrimental to the survival of COAD patients. KEGG pathway analyses indicated that the co-expressed genes ofeFGFfamily members were mainly related to the regulation of the actin cytoskeleton and, more notably, in Ras signaling, PI3k-Akt signaling, Rap1 signaling, and cancer pathways. Based on qRT-PCR results,FGF21was significantly overexpressed in the colon polyps compared to normal mucosa. Additionally, RNA expression ofFGF21andFGF23was markedly elevated in adenomatous polyps as opposed to hyperplastic polyps.ConclusionCollectively, these findings reveal the critical roles ofeFGFsin COAD tumorigenesis and suggesteFGFfamily members as promising prognostic and diagnostic markers for CRC as well as discriminating markers for high-risk from low-risk polyps.