EGFL6 predicts unfavorable prognosis and serves as a potential indicator in esophageal carcinoma

The EGF-like domain multiple 6 (EGFL6) has been documented as an oncogene across diverse cancer types. Despite its known importance in tumorigenesis, EGFL6's involvement in esophageal carcinoma (ESCA) remains largely unexplored. Herein, we integrated multi-source omics data to characterize EGFL6's expression landscape, biological functions, and immunological implications in ESCA-with a focus on its prognostic value.

To identify dysregulated basement membrane-related genes (BMRGs) in ESCA, we performed Venn overlap analysis on RNA-seq data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and a curated BMRG reference list. Weighted gene co-expression analysis (WGCNA) was used to identify EGFL6-related modules and functional enrichment of differentially expressed genes (DEGs) were identified via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). EGFL6-specific epigenetic (DNA methylation) and genetic alterations were validated using Methsurv and cBioPortal. Single-sample GSEA (ssGSEA) was applied to explore immune infiltration and its correlation with EGFL6. Prognostic significance of EGFL6 was examined via Kaplan-Meier and receiver operating characteristic (ROC) analyses.

Venn overlap analysis indicated EGFL6 as a significantly overexpressed gene in ESCA that closely correlated with multiple clinical and pathological features. WGCNA and subsequent functional enrichment analysis revealed that EGFL6-related DEGs participate in critical biological processes. Kaplan-Meier analysis demonstrated that increased EGFL6 contributed to reduced disease-specific survival (DSS) and progression-free interval (PFI) in patients with ESCA. In vitro experiments confirmed that EGFL6 promotes ESCA by enhancing cell proliferation, invasion and regulating cell-cycle progression.

EGFL6 is significantly upregulated in ESCA and is related to various clinical factors, immune modulation and reduced prognosis. EGFL6 could be identified as a novel prognostic biomarker and a viable therapeutic target for the development of personalized treatment approaches in ESCA.