Significance of hydroxymethylglutaryl-CoA synthase 2 on prognosis of esophageal squamous cell carcinoma

Abstract

Objective: To explore the roll and function of hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) in the development and progression of human esophageal squamous cell carcimoma(ESCC). Method: Using immunohistochemistry, the expression of HMGCS2 was determined in 150 primary ESCC patients from July 2002 to December 2005 in the People's Hospital of Linzhou City, Henan Province. And HMGCS2 over-expression ESCC cell lines were established to verify HMGCS2 gene function. Result: In 150 cases of ESCCs, the expression rate of HMGCS2 was 58% (87/150), which was lower than 72% (108/150) in paired normal tissues, the difference was statistically significant (P=0.013). HMGCS2 down-regulated expression was associated with tumor cell differentiation (P=0.022), pT status (P=0.036), pN status (P=0.017) and TNM stage(P=0.012). The 5-years disease-specific survival (DSS) in down HMGCS2 expression group (14 months) was poorer than those in normal expression group (20 months; P=0.002). In addition, multivariate Cox regression analysis showed that HMGCS2 expression (Wald=7.136, P=0.008) was an independent risk factor for DSS. Furthermore, functional studies demonstrated that HMGCS2 gene could suppress the tumorigenic ability of ESCC cells (OD: 0.79±0.04 vs 1.25±0.68; P=0.01), the formation of colone (number of colones: 30±10 vs 189±15, P=0.002), and cell motility (number of cells: 27±14 vs 222±40, P=0.009). Conclusion: HMGCS2 can inhibit the proliferation and migration of ESCC cells, and could be an important candidate tumor suppressor gene for ESCC.