Predictive proteomic signatures for response of pancreatic cancer patients receiving chemotherapy

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