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

Abstract

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

• cancer
• drug sensitivity
• genetic alteration
• HMGCS1
• mevalonate pathway
• prognosis