Abstract
Sirtuin 6 (SIRT6) plays a critical role in the progression and development of gastrointestinal cancers. However, the association between SIRT6 expression and clinicopathological parameters and prognosis in gastrointestinal cancer patients remains inconclusive. Consequently, we conducted this meta-analysis to evaluate the importance of SIRT6 expression in various types of gastrointestinal cancers. PubMed, EMBASE, and Web of Science databases were systematically searched to screen the relevant literature. The reported or estimated hazard ratio (HR) and odds ratio (OR) and their corresponding 95% confidence interval (CI) were pooled to assess the strength of the association. Nine studies involving 867 patients were included in the meta-analysis. Overall analysis showed that high SIRT6 expression was related to better overall survival in gastrointestinal cancers (HR = 0.62, 95% CI = 0.47–0.82). High SIRT6 expression was also related to a favorable tumor node metastasis (TNM) stage (OR = 0.44, 95% CI = 0.28–0.70) among gastrointestinal cancer patients. Our meta-analysis revealed that high SIRT6 expression might be a potential biomarker predicting better prognosis in gastrointestinal cancers, which may offer options for gastrointestinal cancer treatment.
Highlights
Cancers of the digestive system are one of the most common types in aggressive malignancies worldwide.In 2019, almost 3,28,030 new cancer cases and 1,65,460 cancer deaths of the digestive system were assumed to occur in the United States according to the International Agency for Research on Cancer [1]
The results showed that high Sirtuin 6 (SIRT6) expression was related to a favorable tumor node metastasis (TNM) stage (OR = 0.44, 95% confidence interval (CI) = 0.28–0.70, P = 0.001; I2 = 23.7%, P = 0.263, fixed-effects model) (Figure 3 and Table 2)
SIRT6 is closely related to chromatin, deacetylates H3K9 and H3K56, and regulates glucose metabolism, inflammation, gene expression, and genomic stability [25–30], which is cancers including colorectal cancer (CRC), gastric cancer (GC), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC)
Summary
Cancers of the digestive system are one of the most common types in aggressive malignancies worldwide.In 2019, almost 3,28,030 new cancer cases and 1,65,460 cancer deaths of the digestive system were assumed to occur in the United States according to the International Agency for Research on Cancer [1]. Epigenetic alterations including DNA methylation, chromatin remodeling, histone modifications, and noncoding RNAs are a hallmark of gastrointestinal cancers [2]. SIRT1, the most extensively studied member of mammalian SIRTs, deacetylates histone and nonhistone proteins to regulate many biological processes, such as cell stress response, apoptosis, senescence, and DNA repair [5]. SIRT1 is regarded as a prognostic marker for OS in gastrointestinal cancers [6]. SIRT6 and SIRT1 have similar functions, and SIRT6 modulates various physiological processes, including aging, metabolism, telomere maintenance, and genomic DNA stability and repair [7–9]. SIRT6 expression was abnormal in various gastrointestinal tumor tissues, including colorectal cancer [10–14], gastric cancer (GC) [15], pancreatic cancer [16,17], and hepatocellular carcinoma (HCC) [18,19]. The prognostic role of SIRT6 in gastrointestinal cancers remains inconsistent and controversial according to the available evidence [10–12,15,17,18]. It is necessary to perform this meta-analysis to systematically evaluate the relationship between SIRT6 expression and
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