Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor entity, characterized by rapid disease progression, early metastatic dissemination, and late diagnosis at advanced tumor stages. Recently, we explored the clinical impact of several microRNAs (miR) associated with proliferation, epithelial-to-mesenchymal transition (EMT), and chemoresistance in tissue and blood serum specimens of PDAC patients. Here, we evaluated the potential of these miRs as diagnostic and prognostic biomarkers in PDAC in serum exosomes and their respective EpCAM-positive (epithelial cell adhesion molecule) subset. Expression analysis by RT-qRT-PCR (real-time quantitative reverse transcription polymerase chain reaction) revealed an overexpression of miR-200b and miR-200c in serum exosomes of PDAC patients as compared to healthy controls (p < 0.001; p = 0.024) and patients with chronic pancreatitis (p = 0.005; p = 0.19). Receiver operating characteristic (ROC) curve analysis showed that a biomarker panel consisting of miR-200b and miR-200c from total and EpCAM-positive serum exosomes enhanced the diagnostic accuracy of carbohydrate antigen 19-9 (CA.19-9) to 97% (p < 0.0001). Univariate survival analysis revealed a correlation between shorter overall survival (OS) and high expression of miR-200c in total serum exosomes (p = 0.038) and miR-200b in EpCAM-positive serum exosomes (p = 0.032), whereas EpCAM exosomal miR-200b was also indicative of shorter OS in the subgroup of patients treated with curative intent (p = 0.013). Multivariate survival analysis showed that miR-200b derived from EpCAM-positive serum exosomes might serve as an independent prognostic factor in PDAC (p = 0.044). Our findings indicate a potential role of exosomal miR-200 as diagnostic and prognostic liquid biopsy marker in PDAC and call for validation in a larger, multicenter setting.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor entity
Multivariate survival analysis showed that miR-200b derived from EpCAM-positive serum exosomes might serve as an independent prognostic factor in PDAC (p = 0.044)
A total of 89 patients were included in this study, thereof 22 healthy patients, 11 patients with chronic pancreatitis, and 56 patients with PDAC
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor entity. being only the11th most common malignancy in the United States, it ranks third in terms of cancer-related deaths and will account for approximately 45,750 deaths in 2019 with a dismal five-year survival rate below 10% [1].The only potentially curative treatment option is surgical resection, the majority of patients are diagnosed at unresectable stages. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor entity. 11th most common malignancy in the United States, it ranks third in terms of cancer-related deaths and will account for approximately 45,750 deaths in 2019 with a dismal five-year survival rate below 10% [1]. The only potentially curative treatment option is surgical resection, the majority of patients are diagnosed at unresectable stages. Medication-based treatment options for PDAC are limited, and FOLFIRINOX (folinic acid, fluorouracil, irinotecan, oxaliplatin) and gemcitabine-based therapeutic regimens are standards of care in both the (neo-)adjuvant and palliative setting [2]. Response rates are low, and this is attributed to PDAC being a highly chemoresistant tumor type. As opposed to other malignancies, the advances made over recent years in treating PDAC have been marginal
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
