The Prognostic and Clinicopathological Roles of Sirtuin-3 in Various Cancers

PLoS One. 2016 Aug 2;11(8):e0159801. doi: 10.1371/journal.pone.0159801. eCollection 2016.

Abstract

Sirtuin-3 (SIRT3) is a major mitochondrial NAD(+)-dependent deacetylase and plays a key role in the progression and development of human cancers. Although the prognostic and clinicopathological features of SIRT3 expression in various cancers have been investigated by different research groups, however, inconsistent and opposing results can be observed. In this study, we therefore performed a meta-analysis to evaluate the significance of SIRT3 expression in various cancers. Systematic literature searching was performed in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang Data up to November 2015. Total effect analyses and subgroup analyses were performed to evaluate the relationship between SIRT3 expression and overall survival, cancer/non-cancer tissues, lymph node metastasis, pathological differentiation, tumor node metastasis (TNM) stage, tumor size, and gender, in various cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to clarify the risk or hazard association. A total of 14 studies comprising 2165 cancer patients were included to assess the association between SIRT3 immunohistochemical expression and overall survival or clinicopathological characteristics. SIRT3 expression was significantly associated with overall survival in gastric cancer (HR = 0.62, 95% CI = 0.43-0.89, P = 0.009) and hepatocellular carcinoma patients (HR = 0.56, 95% CI = 0.42-0.74, P<0.0001), cancer/non-cancer tissues in hepatocellular carcinoma patients (OR = 0.04, 95% CI = 0.01-0.16, P<0.0001), lymph node metastasis in breast cancer patients (OR = 2.20, 95% CI = 1.49-3.26, P<0.0001), and also pathological differentiation in hepatocellular carcinoma patients (OR = 0.69, 95% CI = 0.48-0.98, P = 0.04) and gastric cancer patients (OR = 0.33, 95% CI = 0.21-0.50, P<0.00001), by subgroup analyses. Furthermore, SIRT3 expression was significantly associated with pathological differentiation in total effect analysis (OR = 0.46, 95% CI = 0.29-0.74, P = 0.001). No detectable relation between SIRT3 expression and other clinicopathological parameters were found. This meta-analysis indicates that SIRT3 expression level is associated with prognostic and clinical features in specific cancers.

Publication types

  • Meta-Analysis

MeSH terms

  • Biomarkers, Tumor / analysis
  • Breast / pathology
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / pathology
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Liver / pathology
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / pathology
  • Lymphatic Metastasis / diagnosis
  • Lymphatic Metastasis / pathology
  • Male
  • Neoplasms / diagnosis*
  • Neoplasms / epidemiology
  • Neoplasms / pathology
  • Prognosis
  • Sirtuin 3 / analysis*
  • Stomach / pathology
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / pathology
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Sirtuin 3

Grant support

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 31271445 and 31170785), the Fund for University Talents of Guangdong Province, the Guangdong Natural Science Foundation of China (No. S2012030006289), and the Department of Education, Guangdong Government under the Top-tier University Development Scheme for Research and Control of Infectious Diseases.