A pan-cancer analysis of the oncogenic role of 7-dehydrocholesterol reductase (DHCR7) in human tumors

Abstract

Background: DHCR7, a switch between cholesterol and vitamin D synthesis that plays a pivotal role in tumorigenesis, is a promising therapeutic target in oncology. Despite increasing strong support for its importance, there is no pan-cancer analysis across multiple databases that can be available for in-depth data mining of the gene. Methods: We first investigated the potential oncogenic roles of DHCR7 based on tumor data from both The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A variety of analytical methods were used to gain a better mechanistic understanding of DHCR7: gene expression, survival situations, genetic mutations, immunocyte infiltration, and correlative cellular pathways. Results: DHCR7 was highly expressed in many cancers, and distinct correlations exist between DHCR7 expression and prognosis of cancer patients. cBioPortal reported that a nonsense mutation of F215L* was considered to be the primary tumorigenic genetic alteration to DHCR7 and was found in cases of LUSC, STAD, and CESC. The DHCR7 expression levels were found to be positively correlated with level of infiltration of cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs) and negatively correlated with anti-tumor immune cells in majority of tumors. The main enrichments for biological processes were steroid biosynthesis, cholesterol metabolic process, and lipid metabolic process for DHCR7. Conclusion: This is the first time to conduct a comprehensive pan-cancer analysis of DHCR7. It provides critical insights into the functions of DHCR7 in tumorigenesis and highlights the potential diagnostic and therapeutic targeted role of DHCR7 for cancers.

Chronic Aripiprazole and Trazodone Polypharmacy Effects on Systemic and Brain Cholesterol Biosynthesis

“…All the data to date would suggest that pronounced elevation of 7-DHC during development (through its oxysterols) is detrimental. In the field of cancer research, DHCR7 expression levels were found to be positively correlated with the infiltration of cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs), and negatively correlated with anti-tumor immune cells in a majority of tumors [ 62 ]. For example, in pancreatic cancer, high DHCR7 gene expression results in shorter survival of patients [ 63 ].…”