The prognostic and clinicopathological roles of sirtuin-6 in various cancers: A meta-analysis

Abstract

Background: SIRT6, a chromatin-associated nuclear protein, exhibits beneficial and pivotal functions in longevity, cardiovascular diseases, and cancer. However, the significant and controversial clinical value of SIRT6 in cancers has not been fully defined. In this manuscript, we performed an updated and comprehensive meta-analysis of all relevant clinical data in order to gain an exhaustive summary of the clinicopathological roles of SIRT6 in various human cancers. Materials and Methods: A systematic literature searching was performed in PubMed, Web of Science, Embase, and CNKI up to April 2019. Studies enrolled in our quantitative meta-analysis were selected according to inclusion and exclusion criteria. Our meta-analysis was performed using total effect analyses and subgroup analyses to evaluate the relationship between SIRT6 expression and overall survival, clinicopathological parameters of multiple types in cancer patients including cancer/noncancer tissues, lymph node metastasis, metastasis, distant metastasis, differentiation, tumor stage and tumor node metastasis (TNM) stage, tumor size, gender, estrogen receptor, and progesterone receptor. The hazard ratios (HRs) or odds ratios (ORs) of the 95% confidence intervals (CIs) were calculated to reveal the risk or hazard association. All analyses were conducted using the Cochrane Collaboration Review Manager 5.3 software. Results: A total of twenty studies comprising 2700 patients from five countries who represented nine cancer types were included to assess the association between SIRT6 immunohistochemical expression and overall survival or clinicopathological characteristics. Cancer type subgroup analysis showed that high SIRT6 expression was associated with worse OS in hepatocellular carcinoma (HR: 1.49, 95% CI: [1.22, 1.81], P < 0.0001, I2 = 0%), osteosarcoma (HR: 2.05, 95% CI: [1.28, 3.30], P = 0.003, I2 = 0%), and non-small cell lung cancer (NSCLC) (HR: 1.88, 95% CI: [1.02, 3.47], P = 0.004, I2 = 73%). In addition, our results demonstrated that SIRT6 expression was statistically significant in noncancer tissues higher than in cancer tissues (OR = 0.32, 95% CI = 0.13–0.79, P = 0.01, random-effects model). Furthermore, it has been shown that SIRT6 expression was well correlated with lymph node metastasis in patients with breast carcinoma (OR = 1.76, 95% CI = 1.17–2.66, P = 0.007, fixed-effects model), the stages of pathological differentiation in cancer patients (OR = 1.53, 95% CI = 1.08–2.18, P = 0.02, fixed-effects model), tumor stages (I–IV) in NSCLC patients (OR = 0.40, 95% CI = 0.20–0.80, P = 0.01, fixed-effects model), and TNM stages in colon cancer patients (OR = 2.41, 95% CI = 1.38–4.20, P = 0.002, fixed-effects model). Nevertheless, there was no detectable correlation between SIRT6 expression and other clinicopathological parameters in total or subgroup analyses. Conclusion: Our current meta-analysis indicates that the expression level of SIRT6 is highly associated with overall survival and clinical features in specific cancers.