Background: Increased risk and cancer-related mortality is observed in pancreatic cancer (PC) patients with diabetes mellitus (DM). Whether using metformin as glucose-lowering therapy can result in survival benefit in this group of patients is still unclear. Methods: A meta-analysis of 21 studies that including 38,772 patients was performed to investigate the association between metformin and overall survival in patients with PC and concurrent DM. Results: A significant survival benefit was observed in metformin treatment group compared with non-metformin group (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.74–0.91). These associations were observed in both subgroups of Asian countries (HR = 0.69, 95% CI: 0.60–0.79) and Western countries (HR = 0.86, 95% CI: 0.76–0.95), the former was more obvious. Survival benefit was gained for patients at early stage (HR = 0.75, 95% CI: 0.64–0.85) and mixed stage (HR = 0.81, 95% CI: 0.70–0.91), but not for patients at advanced stage (HR = 0.99, 95% CI: 0.74–1.24). Similarly, survival benefit was also observed in patients receiving surgery (HR = 0.82, 95% CI: 0.69–0.94) and comprehensive treatment (HR = 0.85, 95% CI: 0.77–0.93), but not in chemotherapy group (HR = 0.99, 95% CI: 0.67–1.30). No obvious benefit was suggested when pooled by time-varying COX model (HR = 0.94, 95% CI: 0.86–1.03). Conclusions: These results suggest that metformin is associated with survival benefit in patients with PC and concurrent DM. Further randomized controlled trials and prospective studies with larger sample sizes are required to confirm our findings.

To identify a gemcitabine resistance-associated gene signature for risk stratification and prognosis prediction in pancreatic cancer. Pearson correlation analysis was performed with gemcitabine half maximal inhibitory concentration (IC50) data of 17 primary pancreatic cancer lines from Genomics of Drug Sensitivity in Cancer (GDSC) and the transcriptomic data from GDSC and Broad Institute Cancer Cell Line Encyclopedia, followed by risk stratification, expression evaluation, overall survival (OS) prediction, clinical data validation and nomogram establishment. Our biomarker discovery effort identified a 14-gene signature, most of which featured differential expression. The 14-gene signature was associated with poor OS in E-MTAB-6134 (HR 2.37; 95% CI 1.75–3.2; p < 0.0001), pancreatic cancer-Canada (PACA-CA) (HR 1.76; 95% CI 1.31–2.37; p = 0.00015), and 4 other independent validation cohorts: pancreatic cancer-Australia (PACA-AU) (HR 1.9; 95% CI 1.38–2.61; p < 0.0001), The Cancer Genome Atlas (TCGA) (HR 1.73; 95% CI 1.11–2.69; p = 0.014), GSE85916 (HR 1.97; 95% CI 1.14–3.42; p = 0.014) and GSE62452 (HR 1.82; 95% CI 1.02–3.24; p = 0.039). Multivariate analysis revealed that the 14-gene risk score was an independent pancreatic cancer outcome predictor in E-MTAB-6134 (p < 0.001) and TCGA (p = 0.006). A nomogram including the 14-gene was established for eventual clinical translation. We identified a novel gemcitabine resistance gene signature for risk stratification and robust categorization of pancreatic cancer patients with poor prognosis.

Background: The relationship between Helicobacter pylori (H. pylori, HP) infection and pancreatic cancer would be investigated in this article.Methods: All cohort studies and case-control studies about H. pylori infection and pancreatic cancer up to October 2021 were searched in the databases of PubMed, Embase and Cochrane. The combined odds ratio (OR) and 95% confidence interval (CI) were calculated by R 4.1.0 software. Funnel plot and Egger test were used to evaluate publication bias.Results: A total of 17 studies which included 8 case-control studies, 5 nested case-control studies, and 4 cohort studies were included in this study, and the results of this article have confirmed that the H. pylori infection was significantly correlated with the occurrence of pancreatic cancer (OR =1.30, 95% CI: 1.02-1.64), especially in economically underdeveloped areas (OR =2.10, 95% CI: 1.44-3.05). However, negative results were obtained in the relationship between CagA + H. pylori and pancreatic cancer. Similarly, we also did not find an association between vacuolating cytotoxin gene A-positive strains (VacA-positive H. pylori) and pancreatic cancer. The heterogeneity of this study was significant. Through a sensitivity analysis by the leaveone-out method, we found the results remained unchanged on the whole but the correlation between H. pylori infection and the occurrence of pancreatic cancer in the Asian population was significant. The tests for funnel plot asymmetry indicated that there might be obvious publication bias in this study. After carrying out the Egger test, we proved the existence of the publication bias in this study, which could have a certain impact on the results.Discussion: Based on the currently available data, we confirm that H. pylori infection can increase the incidence of pancreatic cancer in general. CagA/VacA-positive H. pylori infection is not associated with the incidence of pancreatic cancer. H. pylori infection is significantly associated with the incidence of pancreatic cancer in economically underdeveloped areas, while the relationship between H. pylori infection and the incidence of pancreatic cancer in the Asian population is uncertain. In addition, more high-quality studies are needed to be included to confirm this conclusion.

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The authors have requested that this preprint be withdrawn due to author disagreement.