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Prognostic significance of anti-diabetic medications in pancreatic cancer: A meta-analysis.

ABSTRACT: The role of anti-diabetic medications in pancreatic cancer remains conflicting. We carried out a systematic search of Pubmed and Embase databases for studies published before August 2016, which assessed the associations between anti-diabetic medications (metformin, sulfonylureas, thiazolidinediones and insulin) intake and pancreatic cancer prognosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Fourteen studies enrolling 94778 participants were eligible for inclusion, with 12 cohort studies and 2 randomized controlled trials (RCTs). Significant association between metformin (adjusted HR=0.77, 95% CI=0.68-0.87) use and OS was found in cohort studies, whereas no significant association between metformin use and PFS (HR=1.22; 95% CI=0.76-1.95) or OS (HR=1.20, 95% CI=0.84-1.72) in RCTs. No significant survival benefits were identified for insulin (HR=1.18, 95% CI=0.83-1.69), sulfonylureas (HR=1.03, 95% CI=0.81-1.30), or thiazolidinediones (HR=0.84, 95% CI=0.58-1.22). The trim-and-fill method and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Our findings provide strong evidence that metformin is associated with improved OS in pancreatic cancer patients in cohort studies. However, the effect of other anti-diabetic medications should be interpreted with caution owing to the limited number of studies.

SUBMITTER: Zhou DC

PROVIDER: S-EPMC5617510 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Prognostic significance of anti-diabetic medications in pancreatic cancer: A meta-analysis.

Zhou Dong-Chu DC Gong Hui H Tan Chong-Qing CQ Luo Jian-Quan JQ

Oncotarget 20170509 37

The role of anti-diabetic medications in pancreatic cancer remains conflicting. We carried out a systematic search of Pubmed and Embase databases for studies published before August 2016, which assessed the associations between anti-diabetic medications (metformin, sulfonylureas, thiazolidinediones and insulin) intake and pancreatic cancer prognosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes of interest were overal ...[more]

PMID: 28977950

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Project description:Background:Galectins constitute a family of ?-galactoside-binding proteins, which influence various hallmarks of pancreatic cancer, including cell proliferation, invasion and migration; immune escape; and angiogenesis. Although many studies have concentrated on the role of galectins in pancreatic cancer, the results remain controversial. Hence, we performed a comprehensive meta-analysis to clarify the precise diagnostic and prognostic value of galectins in pancreatic cancer. Methods:PubMed/MEDLINE, EMBASE and Web of Science were used to search related published literature up to July 2019. Pooled hazard ratios (HRs), diagnostic accuracy variables and related 95% confidence intervals (CIs) were calculated using STATA 14.0 software. Results:Eleven studies including 1227 participants met our inclusion criteria. High expression of galectin family was not correlated with overall survival (OS) in pancreatic cancer (HR, 1.19; 95% CI 0.67-2.11). According to subgroup analysis, high levels of galectin-1 were significantly correlated with worse OS in pancreatic cancer (HR, 4.77; 95% CI 2.47-9.21), while high levels of tandem-repeat galectins (galectin-4 or galectin-9) predicted both better OS (HR, 0.63; 95% CI 0.46-0.86) and disease-free survival (DFS) (HR, 0.63; 95% CI 0.48-0.83). The expression levels of galectin-3 did not directly correlate with prognosis (HR, 0.99; 95% CI 0.40-2.46). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratios of galectin-3 were 0.64 (95% CI 0.41-0.82), 0.76 (95% CI 0.59-0.88), 2.70 (95% CI 1.21-6.1), and 0.47 (95% CI 0.23-0.98), respectively. The area under the curve (AUC) of galectin-3 was 0.77. Conclusion:Taken together, our results suggest that high expression of galectin-1 and low levels of galectin-4 or galectin-9 are predictors of worse prognosis in pancreatic cancer patients. The expression of galectin-3 was not directly related to OS and other clinical characteristics. Although galectin-3 exhibited some diagnostic value in patients with pancreatic cancer in this meta-analysis, clinical application prospects remain to be validated. Further studies are warranted to confirm and strengthen these findings.

Project description:BackgroundPancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.MethodsEligible studies were identified and quality was assessed using multiple search strategies (last search May 2021). Data were collected from studies about prognostic significance of altered ATRX/DAXX in PanNETs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.ResultsFourteen studies involving 2313 patients treated for PanNETs were included. After evaluating for publication bias, disease-free survival and relapse-free survival was significantly shortened in patients with altered ATRX/DAXX gene, with combined HR 5.05 (95% confidence interval (CI): 1.58-16.20, P = 0.01) and 3.21 (95% confidence interval (CI): 1.44-7.16, P < 0.01) respectively. However, the combined data showed there were no difference between patients with altered ATRX/DAXX gene or not in overall survival, with a combined HR 0.71 (95% confidence interval (CI): 0.44-1.15, P = 0.23). We also performed a subgroup analysis with metastatic patients in overall survival, showing a combined HR 0.22 (95% confidence interval (CI): 0.11-0.48, P = 0.96). The small number of studies and paucity of multivariate analyses are the limitations of our study.ConclusionsThis is the first rigorous pooled analysis assessing ATRX/DAXX mutation as prognostic biomarkers in PanNETs. Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance.

Dataset Information

Prognostic significance of anti-diabetic medications in pancreatic cancer: A meta-analysis.

Publications

Prognostic significance of anti-diabetic medications in pancreatic cancer: A meta-analysis.

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