Epidemiological Trends and Shared Molecular Signatures of Pancreatic Ductal Adenocarcinoma and Diabetes: An Integrative Analysis Based on Global Burden of Disease and Gene Expression Omnibus Datasets.

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, and diabetes mellitus has been recognized as both a risk factor for and a potential consequence of PDAC. However, the epidemiological trends and shared molecular mechanisms underlying this association are not completely understood.

METHODS

We conducted an integrative analysis combining population-level epidemiological data and transcriptomic datasets. Global trends in PDAC incidence, PDAC-related mortality, and diabetes incidence from 2013 to 2023 were obtained from the Global Burden of Disease (GBD) database. A meta-analysis was performed to quantify the association between diabetes and PDAC risk. In addition, gene expression datasets focusing on PDAC (GSE15471) and type 2 diabetes mellitus (T2DM; GSE20966) were obtained from the Gene Expression Omnibus database, differentially expressed genes were identified, and upregulated genes associated with both PDAC and T2DM were examined using heatmaps.

RESULTS

Continuous increases in global PDAC incidence, mortality due to PDAC, and the incidence of diabetes were identified in the GBD data. The meta-analysis of eight studies demonstrated that diabetes was significantly associated with an increased risk of PDAC (pooled relative risk = 1.94, 95% CI: 1.78-2.11). Transcriptomic analyses identified five genes-FXYD3, LAMC1, MDFIC, SOCS3, and TREM2-that were consistently upregulated in both PDAC and T2DM-affected tissues.

CONCLUSION

This integrative epidemiological and transcriptomic analysis demonstrates that diabetes and PDAC share not only similar global disease trends but also a significant epidemiological association and common molecular alterations. The identified shared genes may represent molecular links between diabetes and PDAC, providing new insights applicable to risk stratification and mechanistic studies.