Wen-Lung Ma
China Medical University Hospital, Taiwan
Title: Cholesterol Import and steroidogenesis are Biosignatures for gastric cancer progression
Biography
Biography: Wen-Lung Ma
Abstract
Androgens, oestrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or studies. This report used a web-based gene survival analyser to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and oestrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/ LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analysing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to /that in normal counterparts, and also promoted progression. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. In addition, this report also described the importance of steroidogenesis biochemical process in disease progression. It is valuable to implement CYP19A1 targeting therapy in gastric cancer patients, working toward unmet medical needs.