Dataset Information

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

ABSTRACT: Background: Silent information regulator 2 homolog 1 (SIRT1) is an evolutionarily conserved enzymes with nicotinamide adenine dinucleotide (NAD)+-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. Methods: 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. Results: 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, P < 0.0001], disease free survival (DFS) (HR = 1.631, 95% CI: 1.250-2.130, P = 0.0003), event free survival (EFS) (HR = 2.534, 95% CI: 1.602-4.009, P = 0.0001), and progress-free survival (PFS) (HR = 3.325 95% CI: 2.762-4.003, P < 0.0001). Elevated SIRT1 level was associated with tumor stage [Relative Risk (RR) = 1.299, 95% CI: 1.114-1.514, P = 0.0008], lymph node metastasis (RR = 1.172, 95% CI: 1.010-1.360, P = 0.0363), and distant metastasis (RR = 1.562, 95% CI: 1.022-2.387, P = 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. Conclusion: 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.

SUBMITTER: Sun M

PROVIDER: S-EPMC6424908 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Sun Min M Du Mengyu M Zhang Wenhua W Xiong Sisi S Gong Xingrui X Lei Peijie P Zha Jin J Zhu Hongrui H Li Heng H Huang Dong D Gu Xinsheng X

Frontiers in endocrinology 20190313

Background: Silent information regulator 2 homolog 1 (SIRT1) is an evolutionarily conserved enzymes with nicotinamide adenine dinucleotide (NAD)+-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. Methods:< ...[more]

PMID: 30930849

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Project description:BackgroundGPRC5A is associated with various cancer initiation and progression. Controversial findings have been reported about GPRC5A prognostic characteristics, and no meta-analysis has been conducted to assess the relationship between GPRC5A and cancer prognosis. Therefore, the objective of this meta-analysis is to evaluate the overall prognostic effectiveness of GPRC5A.MethodsWe first conducted a systematic search in the PubMed, Embase, Web of Science, CNKI, Cochrane, and WangFang databases. The hazard ratio (HR) and odds ratios (OR) with 95% CI were then pooled to assess the associations between GPRC5A expression and overall survival (OS), disease-free survival (DFS), event-free survival (EFS), and clinicopathological characteristics. Chi-squared test and I2 statistics were completed to evaluate the heterogeneity in our study. A random-effects model was used when significant heterogeneity existed (I2>50% and p<0.05); otherwise, we chose the fixed-effect model. Subgroup analysis was stratified by tumor type, region, HR obtained measurements, and sample capacity to explore the source of heterogeneity.ResultsIn total, 15 studies with 624 patients met inclusion criteria of this study. Our results showed that higher expression of GPRC5A is associated with worse OS (HR:1.69 95%CI: 1.20-2.38 I2 = 75.6% p = 0.000), as well as worse EFS (HR:1.45 95%CI: 1.02-1.95 I2 = 0.0% p = 0.354). Subgroup analysis indicated that tumor type might be the source of high heterogeneity. Additionally, cancer patients with enhanced GPRC5A expression were more likely to lymph node metastasis (OR:1.95, 95%CI 1.33-2.86, I2 = 43.9%, p = 0.129) and advanced tumor stage (OR: 1.83, 95%CI 1.15-2.92, I2 = 61.3%, p = 0.035), but not associated with age, sex, differentiation, and distant metastasis.ConclusionGPRC5A can be a promising candidate for predicting medical outcomes and used for accurate diagnosis, prognosis prediction for patients with cancer; however, the predictive value of GPRC5A varies significantly according to cancer type. Further studies for this mechanism will be necessary to reveal novel insights into application of GPRC5A in cancers.

Project description:Background: Although the treatment of cancer has made evident progress, its morbidity and mortality are still high. A tumor marker is a critical indicator for early cancer diagnosis, and timely cancer detection can efficiently help improve the prognosis of patients. Therefore, it is necessary to identify novel markers associated with cancer. LncRNA myocardial infarction associated transcript (MIAT) is a newly identified tumor marker, and in this study, we aimed to explore the relationship between MIAT and clinicopathological features and patient prognosis. Methods: We searched PubMed, Embase, Web of Science, and The Cochrane Library from inception to September 2020 to identify correlational studies. Then, we extracted valid data and used Stata software to make forest plots. We used the hazard ratio (HR) or odds ratio (OR) with 95% CI to evaluate the relationship between aberrant expression of MIAT and patients' prognosis and clinicopathological features. Results: The study included 21 studies, containing 2,048 patients. Meta-analysis showed that overexpression of lncRNA MIAT was associated with poor overall survival (OS) (HR = 1.60, 95% CI, 1.31–1.96, p < 0.001). In addition, high expression of MIAT could forecast tumor size (OR = 2.26, 95% CI 1.34–3.81, p = 0.002), distant metastasis (OR = 2.54, 95% CI 1.84–3.50, p < 0.001), TNM stage (OR = 2.38, 95% CI 1.36–4.18, p = 0.002), lymph node metastasis (OR = 2.59, 95% CI 1.25–5.36, p = 0.011), and the degree of differentiation (OR = 2.65, 95% CI 1.54–4.58, p < 0.001). However, other clinicopathological features, including age (OR = 1.07, 95% CI 0.87–1.32, p = 0.516), gender (OR = 0.95, 95% CI 0.77–1.19, p = 0.668), and histology (OR = 0.72, 95% CI 0.48–1.10, p = 0.128) were not significantly different from high expression of MIAT. Conclusions: Our study showed that overexpression of MIAT is related to poor overall survival and clinicopathological features. MIAT can be considered a novel tumor marker to help diagnose tumors earlier and improve patient prognosis.

Dataset Information

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

Publications

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

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