Effect of ELFN1 on Epithelial-Mesenchymal Transition and Immune Microenvironment in Colon Adenocarcinoma

Background: The upregulation of extracellular leucine-rich repeat fibronectin type III domain containing 1 (ELFN1) has im-plications in various malignancies. Conversely, its vital role in colon adenocarcinoma (COAD) is still not clearly defined. This study aimed to uncover the ELFN1 role in the progression and immuno-microenvironment of COAD.Methods: This study investigated the ELFN1 expression in 398 tissues of COAD vs 39 normal tissues from The Cancer Genome Atlas (TCGA), 18 tissues of colorectal cancer vs paired normal tissues of GSE50760, and across pan-cancer types. Then, associa-tions between ELFN1 and prognosis and clinical features were analyzed using the Kaplan-Meier and Cox regression (multivari-ate) model. Meanwhile, a nomogram was also constructed. The method of gene set enrichment analysis (GSEA) was employed to investigate the pathways related to ELFN1. The data of TCGA-COAD cohort was used to find out the correlations between ELFN1 and immune microenvironment, immunophenoscore (IPS), and tumor mutational burden (TMB).Results: The analysis revealed that ELFN1 levels were significantly high in patients with COAD tissues, involvement of lymph nodes and advanced stages. The higher expression of ELFN1 in patients had the inferior result, and for overall survival (OS), the ELFN1 served as an independent risk predictor. The nomogram showed a good predictive capability in 1-, 3-, and 5-year OS. The result of GSEA exhibited a positive correlation with cancer-related and immunosuppressive pathways, such as myogenesis, epithelial-mesenchymal transition (EMT), angiogenesis, IL6-JAK-STAT3 (Interleukin 6-Janus Kinase 1-Signal Transducer and Activator of Transcription 3) signaling pathway, inflammatory response, and IL2-STAT5 (Interleukin 2-Signal Transducer and Activator Of Transcription 5) pathways by up-regulation of ELFN1. This study focused on exploring the relationship between EMT and ELFN1, as 50% of the total genes were highly significant and positively co-expressed with ELFN1 in this pathway. In addition, an increased ELFN1 was related to a higher Immune/Stromal Score, elevated infiltration levels of macrophages M0 and Tregs, and a lower IPS and TMB.Conclusions: Increased ELFN1 in COAD patients correlated with worse prognosis and may influence the tumor progression by activating EMT and formatting immunosuppressive microenvironment, which may help predict the response to immunotherapy.