Analysis of expression, methylation, and clinical significance of ELTD1 in clear cell renal cell carcinoma based on bioinformatics
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Abstract:
Objective: To investigate the expression and methylation level of epidermal growth factor, latrophilin and seven transmembrane domain-containing 1 (ELTD1) in clear cell renal cell carcinoma (ccRCC) and their correlation with the clinicopathological features and prognosis of patients. Methods: The differential expression and methylation of ELTD1 gene were analyzed with open databases to discuss the correlation between the ELTD1 expression and the clinicopathological characteristics and prognosis of patients. TIMER 2.0 database was adopted to analyze the tumor immune cell infiltration of ccRCC and screen out ELTD1-related immune checkpoint genes. GO function enrichment and KEGG pathway enrichment analysis were also performed. The genes closely related to ELTD1 were identified through gene co-expression analysis. Results: ELTD1 was significantly upregulated in ccRCC (P<0.05), whose expression is negatively correlated with its methylation in TCGA-KIRC (R=-0.37, P<0.01). ELTD1 transcription expression was significantly correlated with age, T stage, M stage and grade (all P<0.01). Higher expression of ELTD1 was closely associated with overall survival (OS) (HR=0.55, P<0.01) and progression-free survival (PFS) (HR=0.63, P<0.01). Upregulation of ELTD1 expression was an independent protective factor in ccRCC. ELTD1 expression was significantly correlated with immune infiltrating of B cells (R=-0.16, P<0.01), CD4+ T cells (R=-0.27, P<0.01), CD8+ T cells (R=-0.25, P<0.01), macrophages (R=-0.31, P<0.01) and neutrophils (R=-0.27, P<0.001), and diverse immune checkpoint genes (all P<0.01). GO function and KEGG pathway enrichment analysis showed that vascular process and tumor-related signaling pathways were enriched in the ELTD1 high expression phenotypes (all P<0.01). Gene co-expression analysis showed that the effect of tumor inhibition was related to the co-expression network. Conclusion: Upregulation of ELTD1 expression and lower methylation level of ELTD1 in ccRCC are indicators of better prognosis and are related to tumor immune infiltration.