Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer that is characterized by its poor prognosis, rapid progression and development of drug resistance. Chemotherapy is a vital treatment option for most of PDAC patients. Stratification of PDAC patients, who would have a higher likelihood of responding to chemotherapy, could facilitate treatment selection and patient management. Methods A quantitative proteomic study was performed to characterize the protein profiles in the plasma of PDAC patients undergoing chemotherapy to determine if specific biomarkers could be used to predict likelihood of therapeutic response. Results By comparing the plasma proteome of the PDAC patients with positive therapeutic response and longer overall survival (Good-responders) to those who did not respond as well with shorter survival time (Limited-responders), we identified differential proteins and protein variants that could effectively segregate Good-responders from Limited-responders. Functional clustering and pathway analysis further suggested that many of these differential proteins were involved in pancreatic tumorigenesis. Four proteins, including vitamin-K dependent protein Z (PZ), sex hormone-binding globulin (SHBG), von Willebrand factor (VWF) and zinc-alpha-2-glycoprotein (AZGP1), were further evaluated as single or composite predictive biomarker with/without inclusion of CA 19-9. A composite biomarker panel that consists of PZ, SHBG, VWF and CA 19-9 demonstrated the best performance in distinguishing Good-responders from Limited-responders. Conclusion Based on the cohort investigated, our data suggested that systemic proteome alterations involved in pathways associated with inflammation, immunoresponse, coagulation and complement cascades may be reporters of chemo-treatment outcome in PDAC patients. For the majority of the patients involved, the panel consisting of PZ, SHBG, VWF and CA 19-9 was able to segregate Good-responders from Limited-responders effectively. Our data also showed that dramatic fluctuations of biomarker concentration in the circulating system of a PDAC patient, which might result from biological heterogeneity or confounding complications, could diminish the performance of a biomarker. Categorization of PDAC patients in terms of their tumor stages and histological types could potentially facilitate patient stratification for treatment.

中文翻译：

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接受化疗的胰腺癌患者反应的预测蛋白质组学特征。

背景 胰腺导管腺癌 (PDAC) 是一种致命的癌症，其特点是预后不良、进展迅速和产生耐药性。化疗是大多数 PDAC 患者的重要治疗选择。PDAC 患者的分层可能对化疗有更高的反应，可以促进治疗选择和患者管理。方法 进行定量蛋白质组学研究以表征接受化疗的 PDAC 患者血浆中的蛋白质谱，以确定特定生物标志物是否可用于预测治疗反应的可能性。结果 通过比较具有积极治疗反应和较长总生存期（良好反应者）和反应不佳且生存时间较短（有限反应者）的 PDAC 患者的血浆蛋白质组，我们确定了差异蛋白质和蛋白质变体，这些蛋白质变体可能有效地将良好响应者与有限响应者区分开来。功能聚类和通路分析进一步表明，许多这些差异蛋白都参与了胰腺肿瘤的发生。四种蛋白质，包括维生素 K 依赖性蛋白 Z (PZ)、性激素结合球蛋白 (SHBG)、血管性血友病因子 (VWF) 和锌-α-2-糖蛋白 (AZGP1)，被进一步评估为单一或复合预测生物标志物包含/不包含 CA 19-9。由 PZ、SHBG、VWF 和 CA 19-9 在区分良好响应者和有限响应者方面表现最佳。结论 基于所研究的队列，我们​​的数据表明，与炎症、免疫反应、凝血和补体级联相关的通路中涉及的全身蛋白质组改变可能是 PDAC 患者化疗结果的报告者。对于所涉及的大多数患者，由 PZ、SHBG、VWF 和 CA 19-9 组成的小组能够有效地将良好反应者与有限反应者区分开来。我们的数据还表明，PDAC 患者循环系统中生物标志物浓度的剧烈波动（可能由生物异质性或混杂并发症引起）可能会降低生物标志物的性能。