Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent

Better preoperative characterization of patients with pancreatic ductal adenocarcinoma (PDAC) would aid in treatment optimization. Extracellular vesicles (EV) are promising, largely unexplored biomarkers in PDAC. This study aimed to evaluate if plasma EV characteristics are associated with PDAC clin...

Full description

Bibliographic Details
Main Authors: David Badovinac, Katja Goričar, Hana Zavrtanik, Miha Petrič, Teja Lavrin, Nina Mavec, Vita Dolžan, Aleš Tomažič, Metka Lenassi
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Journal of Personalized Medicine
Subjects:
Online Access:https://www.mdpi.com/2075-4426/11/2/77
_version_ 1797406219700273152
author David Badovinac
Katja Goričar
Hana Zavrtanik
Miha Petrič
Teja Lavrin
Nina Mavec
Vita Dolžan
Aleš Tomažič
Metka Lenassi
author_facet David Badovinac
Katja Goričar
Hana Zavrtanik
Miha Petrič
Teja Lavrin
Nina Mavec
Vita Dolžan
Aleš Tomažič
Metka Lenassi
author_sort David Badovinac
collection DOAJ
description Better preoperative characterization of patients with pancreatic ductal adenocarcinoma (PDAC) would aid in treatment optimization. Extracellular vesicles (EV) are promising, largely unexplored biomarkers in PDAC. This study aimed to evaluate if plasma EV characteristics are associated with PDAC clinical characteristics and overall survival (OS). The prospective cohort included 34 PDAC patients undergoing surgery with curative intent. Patient data and plasma samples were collected preoperatively, intraoperatively and one month postoperatively. Small plasma EV (sEV) concentration and size were determined by nanoparticle-tracking analysis. A Mann–Whitney test, Spearman’s rho and Cox regression were used in statistical analysis. Preoperatively, patients with poorly differentiated tumors had significantly larger plasma sEVs when compared to patients with well/moderately differentiated tumors (mean diameter 176.9 vs. 149.2 nm, <i>p</i> = 0.021), the sEV size even enabling discrimination of the two groups (AUC = 0.742, 95% CI = 0.560–0.923). Plasma sEV characteristics were also a predictor of OS in multivariable analysis. Patients with a more than 33.8% increase in sEV concentration after one month had 7.2 months shorter median OS (<i>p</i> = 0.002), while patients with a more than 28.0% decrease in sEV size had 9.2 months shorter median OS (<i>p</i> = 0.045). Plasma sEV concentration and size correlate with tumor differentiation and may predict OS in PDAC patients. In the future, plasma sEV characteristics could contribute to improved patient stratification for optimized treatment.
first_indexed 2024-03-09T03:23:16Z
format Article
id doaj.art-1e00f62351cb483b90c6d23259b4ce9e
institution Directory Open Access Journal
issn 2075-4426
language English
last_indexed 2024-03-09T03:23:16Z
publishDate 2021-01-01
publisher MDPI AG
record_format Article
series Journal of Personalized Medicine
spelling doaj.art-1e00f62351cb483b90c6d23259b4ce9e2023-12-03T15:05:31ZengMDPI AGJournal of Personalized Medicine2075-44262021-01-011127710.3390/jpm11020077Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative IntentDavid Badovinac0Katja Goričar1Hana Zavrtanik2Miha Petrič3Teja Lavrin4Nina Mavec5Vita Dolžan6Aleš Tomažič7Metka Lenassi8Department of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, SloveniaInstitute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaDepartment of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, SloveniaDepartment of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, SloveniaInstitute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaInstitute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaInstitute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaDepartment of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, SloveniaInstitute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaBetter preoperative characterization of patients with pancreatic ductal adenocarcinoma (PDAC) would aid in treatment optimization. Extracellular vesicles (EV) are promising, largely unexplored biomarkers in PDAC. This study aimed to evaluate if plasma EV characteristics are associated with PDAC clinical characteristics and overall survival (OS). The prospective cohort included 34 PDAC patients undergoing surgery with curative intent. Patient data and plasma samples were collected preoperatively, intraoperatively and one month postoperatively. Small plasma EV (sEV) concentration and size were determined by nanoparticle-tracking analysis. A Mann–Whitney test, Spearman’s rho and Cox regression were used in statistical analysis. Preoperatively, patients with poorly differentiated tumors had significantly larger plasma sEVs when compared to patients with well/moderately differentiated tumors (mean diameter 176.9 vs. 149.2 nm, <i>p</i> = 0.021), the sEV size even enabling discrimination of the two groups (AUC = 0.742, 95% CI = 0.560–0.923). Plasma sEV characteristics were also a predictor of OS in multivariable analysis. Patients with a more than 33.8% increase in sEV concentration after one month had 7.2 months shorter median OS (<i>p</i> = 0.002), while patients with a more than 28.0% decrease in sEV size had 9.2 months shorter median OS (<i>p</i> = 0.045). Plasma sEV concentration and size correlate with tumor differentiation and may predict OS in PDAC patients. In the future, plasma sEV characteristics could contribute to improved patient stratification for optimized treatment.https://www.mdpi.com/2075-4426/11/2/77pancreatic cancerextracellular vesiclesnanoparticle-tracking analysistumor differentiationoverall survivalplasma biomarkers
spellingShingle David Badovinac
Katja Goričar
Hana Zavrtanik
Miha Petrič
Teja Lavrin
Nina Mavec
Vita Dolžan
Aleš Tomažič
Metka Lenassi
Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent
Journal of Personalized Medicine
pancreatic cancer
extracellular vesicles
nanoparticle-tracking analysis
tumor differentiation
overall survival
plasma biomarkers
title Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent
title_full Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent
title_fullStr Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent
title_full_unstemmed Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent
title_short Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent
title_sort plasma extracellular vesicle characteristics correlate with tumor differentiation and predict overall survival in patients with pancreatic ductal adenocarcinoma undergoing surgery with curative intent
topic pancreatic cancer
extracellular vesicles
nanoparticle-tracking analysis
tumor differentiation
overall survival
plasma biomarkers
url https://www.mdpi.com/2075-4426/11/2/77
work_keys_str_mv AT davidbadovinac plasmaextracellularvesiclecharacteristicscorrelatewithtumordifferentiationandpredictoverallsurvivalinpatientswithpancreaticductaladenocarcinomaundergoingsurgerywithcurativeintent
AT katjagoricar plasmaextracellularvesiclecharacteristicscorrelatewithtumordifferentiationandpredictoverallsurvivalinpatientswithpancreaticductaladenocarcinomaundergoingsurgerywithcurativeintent
AT hanazavrtanik plasmaextracellularvesiclecharacteristicscorrelatewithtumordifferentiationandpredictoverallsurvivalinpatientswithpancreaticductaladenocarcinomaundergoingsurgerywithcurativeintent
AT mihapetric plasmaextracellularvesiclecharacteristicscorrelatewithtumordifferentiationandpredictoverallsurvivalinpatientswithpancreaticductaladenocarcinomaundergoingsurgerywithcurativeintent
AT tejalavrin plasmaextracellularvesiclecharacteristicscorrelatewithtumordifferentiationandpredictoverallsurvivalinpatientswithpancreaticductaladenocarcinomaundergoingsurgerywithcurativeintent
AT ninamavec plasmaextracellularvesiclecharacteristicscorrelatewithtumordifferentiationandpredictoverallsurvivalinpatientswithpancreaticductaladenocarcinomaundergoingsurgerywithcurativeintent
AT vitadolzan plasmaextracellularvesiclecharacteristicscorrelatewithtumordifferentiationandpredictoverallsurvivalinpatientswithpancreaticductaladenocarcinomaundergoingsurgerywithcurativeintent
AT alestomazic plasmaextracellularvesiclecharacteristicscorrelatewithtumordifferentiationandpredictoverallsurvivalinpatientswithpancreaticductaladenocarcinomaundergoingsurgerywithcurativeintent
AT metkalenassi plasmaextracellularvesiclecharacteristicscorrelatewithtumordifferentiationandpredictoverallsurvivalinpatientswithpancreaticductaladenocarcinomaundergoingsurgerywithcurativeintent