Abstract
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.
Highlights
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
In GSE62254, SIRT1 and SIRT2 exerted no associations with the clinical features, SIRT3 was associated with T stage, SIRT4 was associated with pStage, SIRT5 was associated with T stage, SIRT6 was associated with age, M stage, and pStage, and SIRT7 was associated with Lauren classification, N stage, and pStage (Table 1)
The results suggested SIRT4, SIRT6, and SIRT7 were associated with Lauren classification, and SIRT3-5 were associated with pStage (Table 3)
Summary
Still needed and will help to provide better prognosis and individualized treatments. Kaplan-Meier plotter (KM plotter), an online tool, can be utilized to analyze correlations of individual genes with prognosis of patients. This database was initially established using data from a group of 1,809 breast cancer patients [20, 21]. We performed subgroup analyses to explore the effects of clinicopathological features, such as gender, stage, Lauren classification, differentiation, treatment, and HER2 status, on the associations between sirtuins mRNA expression and OS in GC. In patients with stage 1 cancer, significant association was only found between SIRT2 and OS In GC with poor differentiation, significant associations were identified between SIRT4-5 and OS (n = 165 for SIRT4; n = 121 for SIRT5, Table 8).
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