High Endomucin Expression Correlates with a Favorable Immune Landscape and Improved Survival in Clear-Cell Renal Cell Carcinoma (ccRCC) ^†

Endomucin (EMCN) contributes to both cell adhesion and signaling processes, thereby participating in the modulation of immune responses within the vasculature. In this study, we uncover how EMCN modulates the tumor immune microenvironment in clear-cell renal cell carcinoma (ccRCC). The Cancer Genome Atlas (TCGA) was used to obtain clinicopathological and expression data on KIRC. The prognostic significance of EMCN expression in ccRCC was assessed through univariate analysis. DNMIVD was used to investigate the methylation status of EMCN in tumor and normal adjacent tissue (NAT). TCGExplorer was utilized to employ GSEA to identify pathways enriched by the high or low expression of EMCN. Hallmark Gene sets from MSigDB were utilized. The immune microenvironment was evaluated using the Tumor IMmune Estimation Resource (TIMER 2.0). High EMCN expression was associated with heightened overall survival and better survival (HR: 0.60, 95% CI: 0.52–0.68, p < 0.0001) in the TCGA ccRCC cohort. The promoter region of EMCN was hypermethylated in tumor tissue, in contrast to normal adjacent tissue, with an increased beta value of 0.13715 (p < 0.001) associated with decreased expression of EMCN in tumor tissue compared to NAT. The top three enriched GSEA terms when EMCN was highly expressed were hallmark_TGF_beta_signaling, KRAS_signalling_up, and Apical_junction. In contrast, when the expression of EMCN was low, E2F_targets, Oxidative_phosphorylation, and MYC_targets_v2 were the top terms. EMCN expression was positively correlated with resting memory CD4+T cells (ρ = 0.217, p = 2.68e⁻⁶), naïve B cells (ρ = 0.273, p = 2.43e⁻⁹), plasma B cells (ρ = 0.158, p = 6.73e⁻⁴), M1 macrophages (ρ = 0.167, p = 3.05e⁻⁴), Monocytes (ρ = 0.29, p = 2.17e⁻¹⁰), resting NK cells (ρ = 0.208, p = 6.39e⁻⁶), activated mast cells (ρ = 0.373, p = 1.05e⁻¹⁶), and M2 macrophages (ρ = 0.127, p = 6.45e⁻³). It correlated negatively with Tregs (ρ = −0.349, p = 1.23e⁻¹⁴), activated memory CD4+ T cells (ρ = −0.17, p = 2.42e⁻⁴), follicular helper T cells (ρ = −0.209, p = 6.20e⁻⁶), neutrophils (ρ = −0.101, p = 3.07e⁻²), M0 macrophages (ρ = −0.333, p = 2.15e⁻¹³), and memory B cells (ρ = −0.217, p = 2.53e⁻⁶).