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.
摘要：
胰腺导管腺癌（PDAC）的基础亚型和经典亚型在预后和对化疗的反应方面存在显着差异。需要进一步的生物标志物来鉴定PDAC的亚型。我们通过综述文章选择了候选生物标志物。使用生物信息学分析这些候选标记与PDAC分子亚型基因集之间的相关性,确认用于识别经典和基础亚型的生物标志物。随后，纳入了298例PDAC患者，和他们的肿瘤组织使用这些生物标志物进行免疫组织化学分层。生存数据分析，包括Cox比例风险建模。我们的结果表明，KRT5/KRT17/S100A2的成对和三重组合与基底亚型基因集表现出更高的相关系数，而GATA6/HNF4A/TFF1的相应组合与经典亚型基因集显示出更高的相关性。无论是分析不匹配的数据还是倾向匹配的数据，与经典亚型相比，基础亚型的总生存时间显着缩短（p<.001），基础亚型患者也面临较高的死亡风险(HR=4.017,95%CI2.675-6.032,p<.001)。总之,KRT5、KRT17和S100A2的组合表达，以成对和三重组合，独立预测PDAC患者的总生存期较短,并可能确定基底亚型.同样，GATA6、HNF4A、和TFF1，以同样的方式，可能表示经典亚型。在我们的研究中,已建立的生物标志物的联合应用为PDAC患者的预后评估提供了有价值的见解.
