S181 Depression as a Potential Prodrome of Pancreatic Cancer: A Systematic Review of Clinical and Biomarker-Based Evidence

Introduction: Pancreatic cancer (PC) is a highly lethal malignancy, often diagnosed at advanced stages due to the absence of early symptoms. Depression is commonly observed in patients with PC and may precede diagnosis, raising the possibility of a biologically mediated prodromal phase. This systematic review evaluates the temporal association between depression and PC and explores potential underlying biological mechanisms, with a focus on cytokine-related biomarkers. Methods: A systematic review was conducted in accordance with PRISMA guidelines, searching MEDLINE, EMBASE, Web of Science, and Cochrane databases through February 2025. Studies were included if they evaluated adult patients with PC and assessed either psychiatric symptoms or biomarker-mediated pathways. Two reviewers independently conducted study selection, data extraction, and quality appraisal using NIH assessment tools. Results: Of 390 citations screened, 26 studies met inclusion criteria. Reported depression prevalence among PC patients ranged from 3.5% to 51.8%. Multiple studies demonstrated significantly higher depression rates in PC compared to other cancers or non-cancer controls. Six epidemiological studies found depression commonly preceded PC diagnosis, often within 3–6 months. One large U.S. claims-based study (n > 100,000) found stronger associations between depression and PC than with other gastrointestinal cancers (OR 4.6; 95% CI 1.07–19.4). Four biomarker-focused studies reported elevated interleukin-6, C-reactive protein, kynurenine pathway activation, and reduced TGF-β in depressed PC patients, suggesting tumor-driven immune dysregulation. Conclusion: Depression may represent an early clinical indicator of PC, potentially mediated by inflammatory processes. Elevated interleukin-6, C-reactive protein RP, and kynurenine pathway alterations support a biologically plausible mechanism. Future research should prioritize prospective designs and biomarker validation to enable earlier detection and intervention.