Meta-analysis of SIRT1 expression as a prognostic marker for overall survival in gastrointestinal cancer

Abstract

Sirtuin 1 (SIRT1), a well-characterized NAD⁺-dependent histone deacetylase, is generally up-regulated in gastrointestinal cancers. However, the prognostic value of SIRT1 in gastrointestinal cancer remains inconclusive. Therefore, we report a meta-analysis of the association of SIRT1 expression with overall survival (OS) in gastrointestinal cancer. PubMed was systematically searched for studies evaluating the expression of SIRT1 and OS in patients with gastrointestinal cancer. Fifteen studies (six evaluating colorectal cancer, three evaluating hepatocellular carcinoma, three evaluating gastric cancer, and one each evaluating pancreatic cancer, esophageal squamous cell carcinoma, and gastroesophageal junction cancer) with 3,024 patients were finally included. The median percentage of gastrointestinal cancers with high SIRT1 expression was 52.5%. Overall analysis showed an association between high SIRT1 expression and worse OS [summary hazard ratio (sHR) 1.54, 95% confidence intervals (CI) 1.21-1.96] in gastrointestinal cancer. However, heterogeneity was observed across studies, which was mainly attributed to cancer type. Subgroup analysis revealed that SIRT1 was significantly associated with worse OS in non-colorectal gastrointestinal cancer (sHR 1.82, 95% CI 1.50-2.21), in particular in gastric cancer (sHR 3.19, 95% CI 1.97-5.16) and hepatocellular carcinoma (sHR 1.53, 95% CI 1.16-2.01), with no evidence of heterogeneity or bias. However, no association was observed in colorectal cancer (sHR 1.15, 95% CI 0.81-1.62). In conclusion, high SIRT1 expression is a potential marker for poor survival in non-colorectal gastrointestinal cancer, but not in colorectal cancer.