Dual and triple gene combinations of KRT5, KRT17, and S100A2 identify basal-like subtype of pancreatic ductal adenocarcinoma and correlate with survival outcome

Abstract

There is a significant difference in prognosis and response to chemotherapy between basal and classical subtypes of pancreatic ductal adenocarcinoma (PDAC). Further biomarkers are required to identify subtypes of PDAC. We selected candidate biomarkers via review articles. Correlations between these candidate markers and the PDAC molecular subtype gene sets were analyzed using bioinformatics, confirming the biomarkers for identifying classical and basal subtypes. Subsequently, 298 PDAC patients were included, and their tumor tissues were immunohistochemically stratified using these biomarkers. Survival data underwent analysis, including Cox proportional hazards modeling. Our results indicate that the pairwise and triple combinations of KRT5/KRT17/S100A2 exhibit a higher correlation coefficient with the basal-like subtype gene set, whereas the corresponding combinations of GATA6/HNF4A/TFF1 show a higher correlation with the classical subtype gene set. Whether analyzing unmatched or propensity-matched data, the overall survival time was significantly shorter for the basal subtype compared with the classical subtype (p < .001), with basal subtype patients also facing a higher risk of mortality (HR = 4.017, 95% CI 2.675–6.032, p < .001). In conclusion, the combined expression of KRT5, KRT17, and S100A2, in both pairwise and triple combinations, independently predicts shorter overall survival in PDAC patients and likely identifies the basal subtype. Similarly, the combined expression of GATA6, HNF4A, and TFF1, in the same manner, may indicate the classical subtype. In our study, the combined application of established biomarkers offers valuable insights for the prognostic evaluation of PDAC patients.