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Comprehensive Analysis Identifies Endocrine Fibroblast Growth Factors As Promising Prognostic Markers for Colorectal Carcinoma Publisher Pubmed



Rejali L1 ; Piroozkhah M1 ; Jahanbin M2 ; Jalali P1 ; Khanabadi B1 ; Abkenar ED1 ; Asghari Z3 ; Hashemi M2, 4 ; Sadeghi A5 ; Salehi Z6 ; Nazemalhosseinimojarad E5, 7
Authors
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Authors Affiliations
  1. 1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  3. 3. Department of Colorectal Surgery, Medical Science of Shahid, Beheshti University, Tehran, Iran
  4. 4. Farhikhtegan Medical Convergence Sciences Research Centre, Farhikhtegan Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  5. 5. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O. Box: 19857-17411, Yeman Street, Chamran Expressway, Tehran, Iran
  6. 6. Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, P.O. Box: 14114, Karegar Ave., Tehran, Iran
  7. 7. Department of Surgery, Leiden University Medical Center, Leiden, Netherlands

Source: Scientific Reports Published:2024


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. © The Author(s) 2024.