Exploring Gene-Regulatory Networks and Potential Therapeutic Drugs Based on ELF3 Expression in Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a life-threatening malignancy, and there is an urgent need for new biomarkers to improve the prognosis of patients. The expression of ELF3 in CCA tumor and non-tumor tissues was examined in two cohorts. ELF3 expression and the methylation level of its promoter in CCA patients with various clinicopathological features were analyzed using the UALCAN website. Co-expressed genes significantly associated with ELF3 were screened using the LinkedOmics website. A protein-protein interaction (PPI) network for these co-expressed genes was constructed using the STRING website. Core co-expressed genes correlated with ELF3 were identified through random walk with restart (RWR) analysis. GeneMANIA was utilized to analyze the major biological functions within networks of kinases and TFs mediated by ELF3. Potential targeted drugs for CCA treatment were screened using the Connectivity Map (CMAP) database. ELF3 expression in CCA tissue was significantly increased compared with that in normal tissue. Among CCA patients with distinct clinicopathological features, ELF3 expression was notably elevated in tumor tissues compared to normal tissue, while ELF3 promoter's methylation levels in tumor tissue were significantly decreased. In total, 307 co-expressed genes, evidently relevant to ELF3, were identified through LinkedOmics analysis. RWR analysis revealed 61 co-expressed genes closely associated with ELF3. Enrichment analysis indicated that these genes control cell junctions and epithelial cell differentiation. GeneMANIA analysis uncovered that ELF3-involved regulatory networks of kinases and TFs were primarily linked to the regulation of immune cells and cell adhesion. CMAP analysis identified 10 potential small molecules for CCA treatment including 4 existing drugs used for other diseases. ELF3 shows promise as a diagnostic marker for CCA, and the drugs we have identified hold great potential for the treatment of this fatal disease.