Date Published: May 2, 2019
Publisher: Public Library of Science
Author(s): Riccardo Giampieri, Francesco Piva, Giulia Occhipinti, Alessandro Bittoni, Alessandra Righetti, Silvia Pagliaretta, Alberto Murrone, Francesca Bianchi, Consuelo Amantini, Matteo Giulietti, Giulia Ricci, Giovanni Principato, Giorgio Santoni, Rossana Berardi, Stefano Cascinu, Jeffrey Chalmers.
Pancreatic ductal adenocarcinoma is associated to dismal prognosis despite the use of palliative chemotherapy, partly due to the lack of knowledge of biological processes underlying disease progression. Exosomes have been identified as biomarkers sources in different cancer types. Aim of the study was to analyse the contents of circulating exosomes in patients with pancreatic cancer who received palliative chemotherapy.
Patients were submitted to blood sample collection before chemotherapy (T0) and after 3 months (T3). We quantified by an ELISA-based technique specific proteins of cancer-derived exosomes (CD44,CD44v6,EpCAM,CD9,CD81,Tspan8,Integrin α6,Integrin β4,CD24,CXCR4). We correlated the baseline levels of these factors and changes between T3 and T0 and survival outcomes. Survival analyses were performed by Kaplan-Meier method. Correlation was assessed by log-rank test and level of statistical significance was set at 0.05. Multivariate analysis was performed by logistic regression analysis.
Nineteen patients were enrolled. EpCAM T0 levels and increased EpCAM levels from T0 to T3 were those mostly associated with differences in survival. Patients having higher EpCAM had median progression free survival (PFS) of 3.18vs7.31 months (HR:2.82,95%CI:1.03–7.73,p = 0.01). Overall survival (OS) was shorter for patients having higher EpCAM (5.83vs16.45 months,HR:6.16,95%CI:1.93–19.58,p = 0.0001) and also response rates (RR) were worse (20%vs87%,p = 0.015). EpCAM increase during treatment was associated with better median PFS (2.88vs7.31 months,HR:0.24,95%CI:0.04–1.22,p = 0.003). OS was also better (8.75vs11.04 months, HR:0.77,95%CI:0.21–2.73,p = 0.66) and RR were 60%vs20% (p = 0.28). Among clinical factors that might determine changes on PFS and OS, only ECOG PS was associated to significantly worse PFS and OS (p = 0.0137and<0.001 respectively).Multivariate analysis confirmed EpCAM T0 levels and EpCAM T0/T3 changes as independent prognostic factors for PFS. Pancreatic cancer patients exosomes express EpCAM, whose levels change during treatment. This represents a useful prognostic factor and also suggests that future treatment modalities who target EpCAM should be tested in pancreatic cancer patients selected by exosome EpCAM expression.
Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest malignancies known worldwide, with less than 20% one-year survival rate .
Nineteen patients were eligibible for enrollment and partecipated to our study. Patients’ clinical characteristics can be found in Table 1.
Patients with metastatic or locally advanced PDAC exhibit high heterogeneity in clinical behaviour, therefore the identification of prognostic biomarkers might be helpful for the choice of palliative treatments.