Clinical impact of different exosomes’ protein expression in pancreatic ductal carcinoma patients treated with standard first line palliative chemotherapy

Autor: Giulia Ricci, Alessandra Righetti, Alberto Murrone, Francesca Bianchi, Francesco Piva, Consuelo Amantini, Riccardo Giampieri, Giulia Occhipinti, Silvia Pagliaretta, Alessandro Bittoni, Rossana Berardi, Stefano Cascinu, Giovanni Principato, Matteo Giulietti, Giorgio Santoni
Přispěvatelé: Giampieri, R., Piva, F., Occhipinti, G., Bittoni, A., Righetti, A., Pagliaretta, S., Murrone, A., Bianchi, F., Amantini, C., Giulietti, M., Ricci, G., Principato, G., Santoni, G., Berardi, R., Cascinu, S.
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Oncology
Male
Integrins
Colorectal cancer
medicine.medical_treatment
Cancer Treatment
Gene Expression
Kaplan-Meier Estimate
Exosomes
Biochemistry
Metastasis
0302 clinical medicine
Medicine and Health Sciences
Medicine
Enzyme-Linked Immunoassays
Multidisciplinary
Pharmaceutics
Liver Diseases
Middle Aged
Prognosis
Epithelial Cell Adhesion Molecule
Extracellular Matrix
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
Disease Progression
Female
Sample collection
Cellular Structures and Organelles
Research Article
Carcinoma
Pancreatic Ductal
Clinical Oncology
Adult
medicine.medical_specialty
Science
Gastroenterology and Hepatology
Adenocarcinoma
Research and Analysis Methods
Disease-Free Survival
03 medical and health sciences
Cancer Chemotherapy
Drug Therapy
Diagnostic Medicine
Internal medicine
Pancreatic cancer
Carcinoma
Cell Adhesion
Biomarkers
Tumor
Chemotherapy
Humans
Progression-free survival
Vesicles
Immunoassays
Aged
business.industry
Cancer
Biology and Life Sciences
Cell Biology
medicine.disease
Pancreatic Neoplasms
030104 developmental biology
Immunologic Techniques
Clinical Medicine
business
Transcriptome
Biomarkers
Zdroj: PLoS ONE
PLoS ONE, Vol 14, Iss 5, p e0215990 (2019)
ISSN: 1932-6203
Popis: IntroductionPancreatic 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 and methodsPatients 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.ResultsNineteen 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 = 0.0137andConclusionsPancreatic 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.
Databáze: OpenAIRE
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