Expression of HMGCS2 and its correlation with clinopathological characteristics in bladder cancer

Abstract

Objective To explore the expression of 3-hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) and its correlation with the clinicopathological characteristics of patients with bladder cancer. Methods The GEO database was used to screen genes that were significantly differentially expressed between muscle invasive bladder cancer and non-muscle invasive bladder cancer. The survival analysis of the screened public differentially expressed genes was performed by gene expression profiling interactive analysis (GEPIA). The Metascape database was used for the functional enrichment analysis of HMGCS2 and its related genes. The expression of HMGCS2 was detected with immunohistochemical staining in clinical samples from patients with bladder cancer. Chi-square test was used to analyze the relationship between the expression of HMGCS2 and the clinicopathological characteristics, and Cox regression analysis was adopted to verify the prognostic efficacy of HMGCS2. Results The transcriptome data of the GEO database showed HMGCS2 had significantly lower expression in muscle invasive bladder cancer compared with non-muscle invasive bladder cancer (7.42±2.51 vs 9.38±2.78, P < 0.05). The survival analysis of the GEPIA database showed that patients with high expression of HMGCS2 had better prognosis (overall survival: HR=0.6, P=0.028; disease progression-free survival: HR=0.59, P=0.036); KEGG pathway analysis and GO functional enrichment analysis showed that HMGCS2 might be involved in fat metabolism, cell apoptosis and platinum resistance, and exerted effect on the signal transduction of the mTOR pathway. In addition, the Chi-square test showed the expression of HMGCS2 was significantly related to the T stage (P < 0.001), tissue grade (P=0.006), patients' overall survival status (P < 0.001) and patients' disease-free survival status (P < 0.001); Univariate Cox regression analysis showed that HMGCS2 was related to the patients' overall survival rate and the disease progression-free survival rate (OS: HR=0.104, P < 0.001; DFS: HR=0.155, P < 0.001); multivariate Cox regression analysis indicated that HMGCS2 was an independent predictor of the prognostic risk of patients (OS: HR=0.181, P < 0.001; DFS: HR=0.312, P < 0.001). Conclusion HMGCS2 is lowly expressed in muscle invasive bladder cancer, and its low expression is closely related to the poor prognosis of patients.

Keywords

• 3-hydroxymethylglutaryl-coa synthase 2
• bladder cancer
• functional enrichment analysis
• survival analysis
• immunohistochemistry