Association of sirtuins with clinicopathological parameters and overall survival in gastric cancer

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, P = 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, P = 3.6E-15; SIRT3: HR = 1.99, 95% CI = 1.62-2.45, P = 2.6E-11; SIRT4: HR = 1.41, 95% CI = 1.19-1.68, P = 6.6E-05; SIRT6: HR = 2.02, 95% CI = 1.66-2.47, P = 1.7E-12; SIRT7: HR = 1.96, 95% CI = 1.63-2.35, P = 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.