Wu Shuangjie, Jiang Jinghui, Liu Jun, Wang Xinhai, Gan Yu, Tang Yifan
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
Oncotarget. 2017 Aug 3;8(37):62589-62599. doi: 10.18632/oncotarget.19880. eCollection 2017 Sep 22.
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.
沉默调节蛋白1（SIRT1）是一种已被充分表征的依赖烟酰胺腺嘌呤二核苷酸（NAD）的组蛋白脱乙酰酶，在胃肠道癌症中通常上调。然而，SIRT1在胃肠道癌症中的预后价值仍无定论。因此，我们报告一项关于SIRT1表达与胃肠道癌症总生存期（OS）关联的荟萃分析。我们系统检索了PubMed中评估胃肠道癌症患者SIRT1表达和OS的研究。最终纳入了15项研究（6项评估结直肠癌，3项评估肝细胞癌，3项评估胃癌，1项分别评估胰腺癌、食管鳞状细胞癌和胃食管交界癌），共3024例患者。胃肠道癌症中SIRT1高表达的中位百分比为52.5%。总体分析显示，胃肠道癌症中SIRT1高表达与较差的OS相关[汇总风险比（sHR）1.54，95%置信区间（CI）1.21 - 1.96]。然而，各研究间存在异质性，这主要归因于癌症类型。亚组分析显示，SIRT1与非结直肠癌胃肠道癌症较差的OS显著相关（sHR 1.82，95%CI 1.50 - 2.21），尤其是在胃癌（sHR 3.19，95%CI 1.97 - 5.16）和肝细胞癌（sHR 1.53，95%CI 1.16 - 2.01）中，且无异质性或偏倚的证据。然而，在结直肠癌中未观察到关联（sHR 1.15，95%CI 0.81 - 1.62）。总之，SIRT1高表达是非结直肠癌胃肠道癌症患者生存不良的潜在标志物，但在结直肠癌中并非如此。
