Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival

Wei Chun Chang, Shang Fen Huang, Yang Ming Lee, Hsueh Chou Lai, Bi Hua Cheng, Wei Chung Cheng, Jason Yen Ping Ho, Long Bin Jeng, Wen Lung Ma*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

27 Scopus citations

Abstract

Androgens, estrogens, 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 in vivo studies. This report used a web-based gene survival analyzer 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 estrogen 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. Analyzing 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. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoproteinmediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested.

Original languageEnglish
Pages (from-to)692-704
Number of pages13
JournalOncotarget
Volume8
Issue number1
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • CYP19A1
  • Cholesterol
  • Gastric cancer
  • Steroidogenesis

Fingerprint

Dive into the research topics of 'Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival'. Together they form a unique fingerprint.

Cite this