Comprehensive Pan-cancer Analysis and Experimental Verification of EGLN Family: Potential Biomarkers in Cervical Cancer

Background: Hypoxia plays a crucial role in malignant tumor formation, primarily mediated by hypoxia-inducible factors (HIFs). Despite extensive research, the complexities and prognostic implications of the EGLN gene family (EGLN1, EGLN2, EGLN3) in cancers remain unclear. Methods: Utilizing public databases (TCGA, GTEx, TARGET, GEO) and bioinformatics tools, a comprehensive analysis of EGLN genes across various cancer types was conducted. Gene ex-pression, mutation data, stemness scores, and clinical information were integrated to evaluate the mutation landscape, expression levels, and prognostic values of EGLNs. Enrichment and pathway analyses explored EGLN-associated biological processes and functional networks. ssGSEA con-structed EGLN scores for prognostic evaluation. Colocalization analysis combined eQTL and GWAS data to investigate genetic variations in cervical cancer. Immunohistochemistry validated EGLN expression in cervical cancer tissues. Results: EGLN genes showed differential expression across cancer types. EGLN1 overexpres-sion was associated with worse survival in cervical squamous cell carcinoma (CESC), pancreatic adenocarcinoma (PAAD), and neuroblastoma (NB), while EGLN3 was linked to poor survival in CESC, lung adenocarcinoma (LUAD), and kidney cancers. EGLNs also demonstrated varied roles in modulating tumor immune activity and heterogeneity. Conclusion: This study provides new insights into EGLN biology and identifies EGLN1 as a potential biomarker for cervical cancer.