DHCR7 as a Prognostic and Immunological Biomarker in Human Pan‐Cancer: A Comprehensive Evaluation

Background The 7‐Dehydrocholesterol reductase (DHCR7), a critical enzyme catalyzing the final step of the cholesterol biosynthesis pathway, has gained attention for its potential role in tumorigenesis. This study systematically investigated the association between DHCR7 expression and oncogenic processes across multiple cancer types. Methods Multi‐omics data were obtained from The Cancer Genome Atlas ( TCGA ) and Gene Expression Omnibus ( GEO ) repositories. DHCR7 expression patterns were analyzed using Oncomine, TIMER , and GEPIA platforms. Prognostic significance was assessed via Kaplan–Meier plotter and GEPIA . Tumor stage correlations and immune/molecular subtype associations were evaluated using TISIDB . SangerBox facilitated analysis of DHCR7's associations with immune checkpoint ( ICP ) molecules, tumor mutational burden ( TMB ), microsatellite instability ( MSI ), mutant‐allele tumor heterogeneity ( MATH ), neoantigen load, and immune cell infiltration. Results DHCR7 exhibited significant overexpression in most malignancies, correlating with advanced tumor stage ( p < 0.05), metastatic progression, and reduced overall survival ( HR = 1.34, 95% CI : 1.18–1.52). Strong associations emerged between DHCR7 expression and critical immunomodulatory parameters: positive correlations with ICPs ( PD ‐ L1 : r = 0.62, CTLA4 : r = 0.58). Significant links to TMB ( p = 2.1e−5), MSI ( p = 4.3e−4), and MATH ( p = 7.8e−3). Distinct immune infiltration patterns, particularly in bladder carcinoma (BLCA), renal clear cell carcinoma (KIRC), and prostate adenocarcinoma (PRAD). Co‐expression network analysis revealed DHCR7's involvement in immune response regulation (GO:0002764, FDR = 0.003), leukocyte differentiation (GO:0002521, FDR = 0.012), and angiogenesis (GO:0001525, FDR = 0.018). Conclusions These pan‐cancer analyses identify DHCR7 as a multifaceted biomarker with dual prognostic and immunotherapeutic relevance. Its involvement in tumor immune microenvironment modulation suggests potential as a therapeutic target.