Shen Xiaobing, Li Pengfei, Xu Yuchao, Chen Xiaowei, Sun Haixiang, Zhao Ying, Liu Mengqi, Zhang Wenwen
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.
Oncotarget. 2017 Sep 8;8(43):74359-74370. doi: 10.18632/oncotarget.20799. eCollection 2017 Sep 26.
To evaluate the associations of sirtuins (SIRT1-7) with clinicopathological parameters in gastric cancer, sirtuins expression profile in NCBI GEO datasets, GSE62254 and GSE15459, was integrated and analyzed. The results suggested that SIRT4, SIRT6, and SIRT7 were associated with Lauren classification and SIRT3-5 were associated with pStage in gastric cancer. Then an online database derived from 1,065 gastric cancer cases, Kaplan-Meier plotter, was used to explore the associations of the mRNA levels of sirtuins with overall survival in gastric cancer. Survival curves generated from Kaplan-Meier plotter suggested that high expression of SIRT1 mRNA was favorable for overall survival in gastric cancer (SIRT1: HR = 0.64, 95% CI = 0.54-0.76, 2.2E-07), high expressions of SIRT2-4 and SIRT6-7 were poor for overall survival (SIRT2: HR = 2.31, 95% CI = 1.87-2.87, 3.6E-15; SIRT3: HR = 1.99, 95% CI = 1.62-2.45, 2.6E-11; SIRT4: HR = 1.41, 95% CI = 1.19-1.68, 6.6E-05; SIRT6: HR = 2.02, 95% CI = 1.66-2.47, 1.7E-12; SIRT7: HR = 1.96, 95% CI = 1.63-2.35, 2.7E-13), whereas no significant association existed between SIRT5 mRNA expression and overall survival. Further analyses stratified by gender, stages, Lauren classification, differentiation, treatment, and HER2 status were also performed. In summary, high SIRT1 mRNA level was associated with better overall survival, SIRT2-4 and 6-7 were associated with poor overall survival, whereas SIRT5 did not show significant association with overall survival in gastric cancer.
为评估沉默调节蛋白（SIRT1 - 7）与胃癌临床病理参数之间的关联，对NCBI GEO数据集GSE62254和GSE15459中的沉默调节蛋白表达谱进行了整合和分析。结果表明，SIRT4、SIRT6和SIRT7与劳伦分类相关，SIRT3 - 5与胃癌的p分期相关。然后，使用来自1065例胃癌病例的在线数据库Kaplan - Meier plotter，探讨沉默调节蛋白的mRNA水平与胃癌总生存期之间的关联。Kaplan - Meier plotter生成的生存曲线表明，SIRT1 mRNA的高表达有利于胃癌的总生存期（SIRT1：风险比[HR] = 0.64，95%置信区间[CI] = 0.54 - 0.76，P = 2.2×10⁻⁷），SIRT2 - 4和SIRT6 - 7的高表达对总生存期不利（SIRT2：HR = 2.31，95% CI = 1.87 - 2.87，P = 3.6×10⁻¹⁵；SIRT3：HR = 1.99，95% CI = 1.62 - 2.45，P = 2.6×10⁻¹¹；SIRT4：HR = 1.41，95% CI = 1.19 - 1.68，P = 6.6×10⁻⁵；SIRT6：HR = 2.02，95% CI = 1.66 - 2.47，P = 1.7×10⁻¹²；SIRT7：HR = 1.96，95% CI = 1.63 - 2.35，P = 2.7×10⁻¹³），而SIRT5 mRNA表达与总生存期之间不存在显著关联。还按性别、分期、劳伦分类、分化程度、治疗方法和HER2状态进行了进一步分析。总之，SIRT1 mRNA高水平与较好的总生存期相关，SIRT2 - 4和6 - 7与较差的总生存期相关，而SIRT5在胃癌总生存期方面未显示出显著关联。
