Comprehensive analysis identifies endocrine fibroblast growth factors as promising prognostic markers for colorectal carcinoma

Abstract

Endocrine fibroblast growth factors (eFGFs) play essential roles in cellular signaling processes, including development and differentiation, and are implicated in various cancers. However, their precise involvement in colon neoplasia and colon adenocarcinoma (COAD) remains incompletely understood. Here, we conducted a comprehensive investigation utilizing multiple databases to explore the multifaceted characteristics of eFGFs. Through integrated analyses of diverse databases, including TIMER2.0, UALCAN, OncoDB, cBioPortal, LinkedOmics, STRING, htfTarget, mirTarBase, circBank, and DGIdb, we explored eFGFs’ gene expression, DNA methylation, prognostic significance, genetic alterations, gene regulatory networks, functional analysis, and drug interactions in COAD patients. Our findings revealed elevated expression levels of eFGFs in COAD, with aberrant gene expression potentially linked to promoter methylation. Importantly, hypermethylation of FGF21 and FGF23 and downregulation of FGF23 correlated with poor survival outcomes in COAD patients. Functional analyses highlighted the involvement of eFGF genes in Ras signaling, PI3K-Akt signaling, and cancer pathways. Furthermore, we validated our findings through a cross-sectional study by quantitative real-time polymerase chain reaction (qRT-PCR), confirming significant overexpression of FGF21 in colon polyps compared to normal mucosa. Additionally, we observed elevated RNA expression of FGF21 and FGF23 in adenomatous polyps compared to hyperplastic polyps. This study sheds new light on the critical roles of eFGFs in COAD tumorigenesis and underscores their potential as promising prognostic markers for COAD, as well as discriminative markers for distinguishing high-risk from low-risk polyps. These findings provide valuable insights into the complex molecular mechanisms underlying colorectal neoplasia and offer potential avenues for targeted therapeutic strategies.