Prognostic biomarkers for pancreatic ductal adenocarcinoma: A contemporary systematic review and modelling study

BACKGROUNDDespite extensive biomarker discovery efforts in pancreatic ductal adenocarcinoma (PDAC), few biomarkers have been implemented clinically, and outcomes in clinical trials remain modest. AIMTo evaluate prognostic transcriptomic and proteomic biomarkers in PDAC, assess clinical trial integration, and develop an exploratory molecular prognostic signature. METHODSA systematic review of studies published between 1 January 2025 and 6 March 2026 was conducted.Eligible studies evaluated tumor-derived transcriptomic or proteomic biomarkers in multivariable survival analyses or clinical trials.In parallel, Clinical Proteomic Tumor Analysis Consortium PDAC data were analyzed to identify candidate proteins.The corresponding genes were evaluated using least absolute shrinkage and selection operator (LASSO) Cox regression in The Cancer Genome Atlas pancreatic adenocarcinoma cohort to develop a prognostic signature, externally validated in GSE71729. RESULTSA total of 71 records met the predefined eligibility criteria, comprising 57 biomarker studies and 14 clinical trials.All 57 biomarker studies reported independent prognostic associations in adjusted multivariable models.None of the 14 clinical trials incorporated molecular biomarkers to determine eligibility, stratify randomization, or define a prespecified endpoint, indicating a substantial translational gap.The resulting 5-gene LASSO signature showed a strong association with overall survival in the derivation cohort but only modest discrimination.Its prespecified continuous risk score failed external validation.Although median-4 / 81 based risk stratification in the validation cohort was nominally significant, the association did not remain significant after correction for threshold selection. CONCLUSIONThe 5-gene signature in this study failed external validation.Contemporary PDAC biomarker discovery has not yet produced clinically reproducible prognostic tools.