Pan-cancer analysis reveals the oncogenic role of 3-hydroxy-3-methylglutaryl-CoA synthase 1

Cancer Rep (Hoboken). 2022 Sep;5(9):e1562. doi: 10.1002/cnr2.1562. Epub 2021 Sep 22.

Abstract

Background: Emerging studies reveals that 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) plays vital oncogenic roles in a broad spectrum of human cancers, but there is no pan-cancer evidence on the relationship between HMGCS1 and various tumor types.

Aim: To explore the potential role of HMGCS1 across various tumor types based on big clinical data.

Methods: We conducted a pan-cancer analysis across more than 30 tumor types, based on the most comprehensive database available, including TCGA, GSCA, clinical proteomic tumor analysis consortium, Kaplan-Meier Plotter dataset, GEPIA2, TIMER2, STRING, and GDSC dataset.

Results: HMGCS1 was highly expressed and negatively correlated with the prognosis in most cancer types. The infiltration levels of cancer associated fibroblast and CD8+ T-cell were closely associated with HMGCS1 expression. Amplification was the most common genetic alteration of HMGCS1 in different cancers, while the frequency of mutation was low. Besides, ACAT2 and MVD were closely correlated and bind to HMGCS1. Pathway enrichment analysis indicated that HMGCS1 was actively involved in steroid biosynthesis. Moreover, high HMGCS1 expression could reduce the sensitivity to most drugs in the GDSC dataset.

Conclusions: Our study revealed the potential oncogenic role of HMGCS1 in cancers.

Keywords: HMGCS1; cancer; drug sensitivity; genetic alteration; mevalonate pathway; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Humans
  • Hydroxymethylglutaryl-CoA Synthase / genetics
  • Hydroxymethylglutaryl-CoA Synthase / metabolism*
  • Proteomics*

Substances

  • Acyl Coenzyme A
  • 3-hydroxy-3-methylglutaryl-coenzyme A
  • HMGCS1 protein, human
  • Hydroxymethylglutaryl-CoA Synthase