Loss of ACSS2 expression predicts poor prognosis in patients with gastric cancer.

Abstract

BACKGROUND: Recent studies have demonstrated that acetyl-CoA synthetase 2 (ACSS2) plays a critical role in cancer cell survival; however, the role of ACSS2 in gastric carcinogenesis has not been determined.

METHODS: We investigated the expression of ACSS2 in human gastric cancer (GC) tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance.

RESULTS: Among 350 GCs, 219 cases (62.6%) were classified as ACSS2-low, whereas 131 cases (37.4%) were ACSS2-high. Loss of ACSS2 expression (ACSS2-low) was more frequently observed in undifferentiated histology (P = 0.002), in cases with MLH1-loss (P = 0.003), and in cases with SIRT3-low (P < 0.001). The ACSS2-low cases showed significantly lower mean disease-free survival (DFS, 68.5 vs. 81.8 months; P = 0.025) and overall survival (OS, 73.5 vs. 86.6 months; P = 0.029). In multivariate analysis, loss of ACSS2 expression was identified as one of the independent prognostic factors predicting worse DFS (HR: 1.547, P = 0.018) and OS (HR: 1.476, P = 0.036).

CONCLUSIONS: We revealed that the loss of ACSS2 expression is a reliable independent poor prognostic factor in GC. Our results may expand our understanding of the involvement of glucose metabolism, including the role of ACSS2, in the pathogenesis of GC.