Plasma Extracellular Vesicle Characteristics as Biomarkers of Resectability and Radicality of Surgical Resection in Pancreatic Cancer—A Prospective Cohort Study

Due to possible diagnostic misjudgment of tumor resectability, patients with pancreatic ductal adenocarcinoma (PDAC) might be exposed to non-radical resection or unnecessary laparotomy. With small extracellular vesicles (sEV) obtained by liquid biopsy, we aimed to evaluate their potential as biomark...

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Main Authors: David Badovinac, Katja Goričar, Teja Lavrin, Hana Zavrtanik, Vita Dolžan, Metka Lenassi, Aleš Tomažič
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/3/605
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author David Badovinac
Katja Goričar
Teja Lavrin
Hana Zavrtanik
Vita Dolžan
Metka Lenassi
Aleš Tomažič
author_facet David Badovinac
Katja Goričar
Teja Lavrin
Hana Zavrtanik
Vita Dolžan
Metka Lenassi
Aleš Tomažič
author_sort David Badovinac
collection DOAJ
description Due to possible diagnostic misjudgment of tumor resectability, patients with pancreatic ductal adenocarcinoma (PDAC) might be exposed to non-radical resection or unnecessary laparotomy. With small extracellular vesicles (sEV) obtained by liquid biopsy, we aimed to evaluate their potential as biomarkers of tumor resectability, radicality of resection and overall survival (OS). Our prospective study included 83 PDAC patients undergoing surgery with curative intent followed-up longitudinally. sEV were isolated from plasma, and their concentration and size were determined. Fifty patients underwent PDAC resection, and thirty-three had no resection. Preoperatively, patients undergoing resection had higher sEV concentrations than those without resection (<i>p</i> = 0.023). Resection was predicted at the cutoff value of 1.88 × 10<sup>9</sup>/mL for preoperative sEV concentration (<i>p</i> = 0.023) and the cutoff value of 194.8 nm for preoperative mean diameter (<i>p</i> = 0.057). Furthermore, patients with R0 resection demonstrated higher preoperative plasma sEV concentrations than patients with R1/R2 resection (<i>p</i> = 0.014). If sEV concentration was above 1.88 × 10<sup>9</sup>/mL or if the mean diameter was below 194.8 nm, patients had significantly longer OS (<i>p</i> = 0.018 and <i>p</i> = 0.030, respectively). Our proof-of-principle study identified preoperative sEV characteristics as putative biomarkers of feasibility and radicality of PDAC resection that also enable discrimination of patients with worse OS. Liquid biopsy with sEV could aid in PDAC patient stratification and treatment optimization in the future.
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spelling doaj.art-c8b950de163b446bace45770117438022023-11-16T16:14:34ZengMDPI AGCancers2072-66942023-01-0115360510.3390/cancers15030605Plasma Extracellular Vesicle Characteristics as Biomarkers of Resectability and Radicality of Surgical Resection in Pancreatic Cancer—A Prospective Cohort StudyDavid Badovinac0Katja Goričar1Teja Lavrin2Hana Zavrtanik3Vita Dolžan4Metka Lenassi5Aleš Tomažič6Department 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, 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, SloveniaDepartment of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, SloveniaDue to possible diagnostic misjudgment of tumor resectability, patients with pancreatic ductal adenocarcinoma (PDAC) might be exposed to non-radical resection or unnecessary laparotomy. With small extracellular vesicles (sEV) obtained by liquid biopsy, we aimed to evaluate their potential as biomarkers of tumor resectability, radicality of resection and overall survival (OS). Our prospective study included 83 PDAC patients undergoing surgery with curative intent followed-up longitudinally. sEV were isolated from plasma, and their concentration and size were determined. Fifty patients underwent PDAC resection, and thirty-three had no resection. Preoperatively, patients undergoing resection had higher sEV concentrations than those without resection (<i>p</i> = 0.023). Resection was predicted at the cutoff value of 1.88 × 10<sup>9</sup>/mL for preoperative sEV concentration (<i>p</i> = 0.023) and the cutoff value of 194.8 nm for preoperative mean diameter (<i>p</i> = 0.057). Furthermore, patients with R0 resection demonstrated higher preoperative plasma sEV concentrations than patients with R1/R2 resection (<i>p</i> = 0.014). If sEV concentration was above 1.88 × 10<sup>9</sup>/mL or if the mean diameter was below 194.8 nm, patients had significantly longer OS (<i>p</i> = 0.018 and <i>p</i> = 0.030, respectively). Our proof-of-principle study identified preoperative sEV characteristics as putative biomarkers of feasibility and radicality of PDAC resection that also enable discrimination of patients with worse OS. Liquid biopsy with sEV could aid in PDAC patient stratification and treatment optimization in the future.https://www.mdpi.com/2072-6694/15/3/605liquid biopsybiomarkersextracellular vesiclespancreatic ductal adenocarcinomaresectionpatient stratification
spellingShingle David Badovinac
Katja Goričar
Teja Lavrin
Hana Zavrtanik
Vita Dolžan
Metka Lenassi
Aleš Tomažič
Plasma Extracellular Vesicle Characteristics as Biomarkers of Resectability and Radicality of Surgical Resection in Pancreatic Cancer—A Prospective Cohort Study
Cancers
liquid biopsy
biomarkers
extracellular vesicles
pancreatic ductal adenocarcinoma
resection
patient stratification
title Plasma Extracellular Vesicle Characteristics as Biomarkers of Resectability and Radicality of Surgical Resection in Pancreatic Cancer—A Prospective Cohort Study
title_full Plasma Extracellular Vesicle Characteristics as Biomarkers of Resectability and Radicality of Surgical Resection in Pancreatic Cancer—A Prospective Cohort Study
title_fullStr Plasma Extracellular Vesicle Characteristics as Biomarkers of Resectability and Radicality of Surgical Resection in Pancreatic Cancer—A Prospective Cohort Study
title_full_unstemmed Plasma Extracellular Vesicle Characteristics as Biomarkers of Resectability and Radicality of Surgical Resection in Pancreatic Cancer—A Prospective Cohort Study
title_short Plasma Extracellular Vesicle Characteristics as Biomarkers of Resectability and Radicality of Surgical Resection in Pancreatic Cancer—A Prospective Cohort Study
title_sort plasma extracellular vesicle characteristics as biomarkers of resectability and radicality of surgical resection in pancreatic cancer a prospective cohort study
topic liquid biopsy
biomarkers
extracellular vesicles
pancreatic ductal adenocarcinoma
resection
patient stratification
url https://www.mdpi.com/2072-6694/15/3/605
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