7-Dehydrocholesterol Reductase is a Promising Prognostic and Immune Biomarker in Pan-Cancer

Abstract

Xianghua Wu, Weiwei Zheng, Li Wang, Xuzhao Zhang, Dan Lin and Zhaoxing Wu

Background: 7-Dehydrocholesterol Reductase (DHCR7) is a key enzyme involving the final step of cholesterol synthesis path- way. Abnormalities in the DHCR7 gene can lead to a variety of diseases, such as Smith-Lemli-Opitz syndrome. However, the relationship between DHCR7 and oncogenesis remain unclear.

Methods: We used several bioinformatic databases which the original data from the TCGA and GEO database. Briefly, the gene of DHCR7 expression were explored by the Oncomine, TIMER and GEPIA databases. The effect of DHCR7 on prognosis was analyzed via Kaplan-Meier plotter and GEPIA database. The TISIDB database was used to determine the relationship between DHCR7 expression and pan-cancer stages and the DHCR7 expression in different immune and molecular subtypes of human cancers. The correlations between DHCR7 expression and Immune Checkpoints (ICP), Tumor Mutational Burden (TMB), Mi- crosatellite Instability (MSI), Mutant-Allele Tumor Heterogeneity (MATH), neoantigens and infiltrating immune cells of human cancers and urogenital cancers were analyzed through the SangerBox database (http://vip.sangerbox.com/login.html). The genomic alterations of DHCR7 were analyzed by the c-BioPortal database. The differential expression of DHCR7 in urogenital cancers with different clinical characteristics was analyzed with the UALCAN database. The DHCR7 co-expression genes in BLCA was analyzed through the Linked Omics database. And the association between DHCR7 and related genes and markers of immune cells were analyzed by TIMER database.

Results: The results indicated that DHCR7 was highly expressed in most cancers, except in Cholangio carcinoma, Pheochromo- cytoma and Paraganglioma. Aberrantly expressed DHCR7 was associated with the poor prognosis, advanced tumor stage and metastasis in most tumor types. Additionally, significant strong correlations between DHCR7 expression and tumor immune-in- filtrated cells (TILs), ICP, TMB, MSI, MATH and neoantigens showed in most human cancers, and marker genes of TILs were significantly related to DHCR7 expression in BLCA, KIRC and PRAD. DHCR7 co-expression networks mostly participated in the regulation of immune response regulating signaling pathway, leukocyte differentiation and angiogenesis.

Conclusion: Through pan-cancer analysis, DHCR7 may serve as a potential prognostic and immunological pan-cancer bio- marker, especially in urological tumors.

PDF