AUTHOR=Sun Min , Du Mengyu , Zhang Wenhua , Xiong Sisi , Gong Xingrui , Lei Peijie , Zha Jin , Zhu Hongrui , Li Heng , Huang Dong , Gu Xinsheng 

TITLE=Survival and Clinicopathological Significance of SIRT1 Expression in Cancers: A Meta-Analysis

JOURNAL=Frontiers in Endocrinology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00121

DOI=10.3389/fendo.2019.00121

ISSN=1664-2392

ABSTRACT=<p><bold>Background:</bold> Silent information regulator 2 homolog 1 (SIRT1) is an evolutionarily conserved enzymes with nicotinamide adenine dinucleotide (NAD)<sup>+</sup>-dependent deacetylase activity. SIRT1 is involved in a large variety of cellular processes, such as genomic stability, energy metabolism, senescence, gene transcription, and oxidative stress. SIRT1 has long been recognized as both a tumor promoter and tumor suppressor. Its prognostic role in cancers remains controversial.</p><p><bold>Methods:</bold> A meta-analysis of 13,138 subjects in 63 articles from PubMed, EMBASE, and Cochrane Library was performed to evaluate survival and clinicopathological significance of SIRT1 expression in various cancers.</p><p><bold>Results:</bold> The pooled results of meta-analysis showed that elevated expression of SIRT1 implies a poor overall survival (OS) of cancer patients [Hazard Ratio (HR) = 1.566, 95% CI: 1.293–1.895, <italic>P</italic> &lt; 0.0001], disease free survival (DFS) (HR = 1.631, 95% CI: 1.250–2.130, <italic>P</italic> = 0.0003), event free survival (EFS) (HR = 2.534, 95% CI: 1.602–4.009, <italic>P</italic> = 0.0001), and progress-free survival (PFS) (HR = 3.325 95% CI: 2.762–4.003, <italic>P</italic> &lt; 0.0001). Elevated SIRT1 level was associated with tumor stage [Relative Risk (RR) = 1.299, 95% CI: 1.114–1.514, <italic>P</italic> = 0.0008], lymph node metastasis (RR = 1.172, 95% CI: 1.010–1.360, <italic>P</italic> = 0.0363), and distant metastasis (RR = 1.562, 95% CI: 1.022–2.387, <italic>P</italic> = 0.0392). Meta-regression and subgroup analysis revealed that ethnic background has influence on the role of SIRT1 expression in predicting survival and clinicopathological characteristics of cancers. Overexpression of SIRT1 predicted a worse OS and higher TNM stage and lymphatic metastasis in Asian population especially in China.</p><p><bold>Conclusion:</bold> Our data suggested that elevated expression of SIRT1 predicted a poor OS, DFS, EFS, PFS, but not for recurrence-free survival (RFS) and cancer-specific survival (CCS). SIRT1 overexpression was associated with higher tumor stage, lymph node metastasis, and distant metastasis. SIRT1-mediated molecular events and biological processes could be an underlying mechanism for metastasis and SIRT1 is a therapeutic target for inhibiting metastasis, leading to good prognosis.</p>