Abstract
BACKGROUND: Extracellular leucine rich repeat and fibronectin type III domain containing 1 (ELFN1), a transmembrane protein implicated in tumorigenesis and therapy resistance, remains mechanistically undefined as a pan-cancer target. In this study, we aimed to elucidate the function and potential mechanism of action of ELFN1 across cancers. METHODS: Through integrative analysis of TCGA and GTEx datasets, we systematically characterized ELFN1 across 33 cancer types, including its expression patterns, prognostic value, mutation landscape, methylation modifications, protein-protein interaction (PPI) networks, and the relationship between ELFN1 expression and immune infiltration. KEGG enrichment analysis was also performed to predict the functions and associated cellular pathways of ELFN1. In addition, the molecular docking tool was used to analyze the affinities between ELFN1 protein and drugs. Finally, we assessed the effect of ELFN1 knockdown on colorectal cancer (CRC) cells using in vitro experiments. RESULTS: Our study revealed significant dysregulation of ELFN1 across various cancer types, with notable diagnostic and prognostic utility in most cancers analyzed. Mechanistically, ELFN1 expression was associated with DNA methylation, DNA repair, genomic instability, and tumor microenvironment (TME) scores in multiple cancer types. Furthermore, Drug sensitivity profiling linked ELFN1 to ABT-737 susceptibility and benzaldehyde resistance through molecular docking. In CRC cells, ELFN1 knockdown significantly inhibited tumor proliferation, migration, and motility. CONCLUSION: The expression level of ELFN1 may provide insights into tumor development and progression in multiple cancers, including CRC, highlighting its potential utility as an effective prognostic biomarkers and immunotherapeutic targets.