Abstract
The clinical value of SIRT1 in hepatocellular carcinoma (HCC) remains controversial. This meta-analysis was performed to investigate the prognostic and clinicopathological significance of the histone deacetylase SIRT1 in HCC. Pooled hazard ratios (HRs) for survival outcomes and pooled odds ratios (ORs) for clinical parameters associated with SIRT1 were calculated in nine studies using Review Manager. Meta-analysis showed that increased SIRT1 expression is associated with poor overall survival (OS) (HR=1.82, 95% confidence interval (CI): 1.49-2.22, P<0.00001) and disease-free survival (DFS) (HR=1.44, 95%CI: 1.06-1.96, P=0.02) in HCC. Increased expression of SIRT1 is more common in female than male HCC patients (OR=0.47, 95%CI: 0.32-0.70, P=0.0001). The increased SIRT1 expression correlates with hepatitis B virus (HBV) infection (OR=1.63, 95%CI: 1.04-2.57, P=0.03), large tumor size (OR=1.81, 95%CI: 1.05-3.13, P=0.03), high p53 expression (OR=2.71, 95%CI: 1.39-5.29, P=0.003), high levels of alpha-fetoprotein (AFP; cutoff value: 400 ng/ml, OR=1.84, 95%CI: 1.26-2.69, P=0.002), and tumor stage (OR=1.72, 95%CI: 1.27-2.32, P=0.0004). Re-sampling statistics for 5,000,000 samples revealed that increased SIRT1 expression is associated with higher TNM stage (OR=1.70, 95%CI: 1.69-1.70, P<0.00001). These results indicate that SIRT1 is a new biomarker off HCC as well as a potentially effective therapeutic target.
Highlights
Primary liver cancer is the sixth most commonly occurring cancer in the world, and the second largest contributor to cancer mortality [1]
In Oncomine and The Cancer Genome Atlas (TCGA) database, no data about Silent information regulator 1 (SIRT1) amplification changes in hepatocellular carcinoma (HCC) were reported (Supplementary Figure S1). 363 studies remained after excluding duplicate studies. 354 studies were excluded because they contained no relevant survival or clinical data (Figure 1)
Eight studies reported the association between SIRT1 high expression and poor prognosis in HCC
Summary
Primary liver cancer is the sixth most commonly occurring cancer in the world, and the second largest contributor to cancer mortality [1]. SIRT1 promotes or inhibits many biological processes, including regulation of gene expression, cellular metabolism, stress response, aging, and chemo-resistance [7]. SIRT1 is thought to promote HCC tumorigenesis. Recent studies have demonstrated that compared with normal liver or surrounding tumor tissues, SIRT1 is strongly overexpressed in human HCC [6, 7]. In HCC, SIRT1 can activate telomerase reverse transcriptase (TERT) gene promoter [10], promote YAP/ TEAD4 association [11], and stabilize c-Myc protein [12]. Recent studies have indicated that increased SIRT1 expression is associated with poor HCC prognosis [7,8,9, 16,17,18,19,20,21]. We speculated that there might be a significant correlation between the expression of SIRT1 and the clinical outcomes of HCC
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