Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very unfavorable prognosis. Surgical resection represents the only potentially curative treatment option, but recurrence after complete resection is almost certain. In an exploratory attempt we here aimed at identifying preoperativ...

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Autores principales:	Marie-Claire Rittmann, Saskia Hussung, Lukas M. Braun, Rhena F. U. Klar, Esther A. Biesel, Stefan Fichtner-Feigl, Ralph Fritsch, Uwe A. Wittel, Dietrich A. Ruess
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eed841e9d8bb480f8aa6de85bb380eea
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spelling	oai:doaj.org-article:eed841e9d8bb480f8aa6de85bb380eea2021-12-02T18:15:24ZPlasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma10.1038/s41598-021-86779-x2045-2322https://doaj.org/article/eed841e9d8bb480f8aa6de85bb380eea2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86779-xhttps://doaj.org/toc/2045-2322Abstract Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very unfavorable prognosis. Surgical resection represents the only potentially curative treatment option, but recurrence after complete resection is almost certain. In an exploratory attempt we here aimed at identifying preoperative plasma protein biomarkers with the potential to predict early recurrence after resection of PDAC. Peripheral blood samples from 14 PDAC patients divided into three groups according to their time to tumor recurrence after curatively intended resection (early: < 6 months, medium: 6–12 months, late: > 12 months) underwent targeted proteome analysis. Proteins most strongly discriminating early and late recurrence were then examined in a number of established PDAC cell lines and their culture supernatants. Finally, PDAC organoid lines from primary tumors of patients with early and late recurrence were analyzed for confirmation and validation of results. In total, 23 proteins showed differential abundance in perioperative plasma from PDAC patients with early recurrence when compared to patients with late recurrence. Following confirmation of expression on a transcriptional and translational level in PDAC cell lines we further focused on three upregulated (MAEA, NT5E, AZU1) and two downregulated proteins (ATP6AP2, MICA). Increased expression of NT5E was confirmed in a subset of PDAC organoid cultures from tumors with early recurrence. MICA expression was heterogeneous and ATP6AP2 levels were very similar in both organoids from early and late recurrent tumors. Most strikingly, we observed high MAEA expression in all tested PDAC (n = 7) compared to a non-cancer ductal organoid line. MAEA also demonstrated potential to discriminate early recurrence from late recurrence PDAC organoids. Our study suggests that identification of plasma protein biomarkers released by tumor cells may be feasible and of value to predict the clinical course of patients. Prediction of recurrence dynamics would help to stratify up-front resectable PDAC patients for neoadjuvant chemotherapy approaches in an individualized fashion. Here, MAEA and NT5E were the most promising candidates for further evaluation.Marie-Claire RittmannSaskia HussungLukas M. BraunRhena F. U. KlarEsther A. BieselStefan Fichtner-FeiglRalph FritschUwe A. WittelDietrich A. RuessNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marie-Claire Rittmann Saskia Hussung Lukas M. Braun Rhena F. U. Klar Esther A. Biesel Stefan Fichtner-Feigl Ralph Fritsch Uwe A. Wittel Dietrich A. Ruess Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma
description	Abstract Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very unfavorable prognosis. Surgical resection represents the only potentially curative treatment option, but recurrence after complete resection is almost certain. In an exploratory attempt we here aimed at identifying preoperative plasma protein biomarkers with the potential to predict early recurrence after resection of PDAC. Peripheral blood samples from 14 PDAC patients divided into three groups according to their time to tumor recurrence after curatively intended resection (early: < 6 months, medium: 6–12 months, late: > 12 months) underwent targeted proteome analysis. Proteins most strongly discriminating early and late recurrence were then examined in a number of established PDAC cell lines and their culture supernatants. Finally, PDAC organoid lines from primary tumors of patients with early and late recurrence were analyzed for confirmation and validation of results. In total, 23 proteins showed differential abundance in perioperative plasma from PDAC patients with early recurrence when compared to patients with late recurrence. Following confirmation of expression on a transcriptional and translational level in PDAC cell lines we further focused on three upregulated (MAEA, NT5E, AZU1) and two downregulated proteins (ATP6AP2, MICA). Increased expression of NT5E was confirmed in a subset of PDAC organoid cultures from tumors with early recurrence. MICA expression was heterogeneous and ATP6AP2 levels were very similar in both organoids from early and late recurrent tumors. Most strikingly, we observed high MAEA expression in all tested PDAC (n = 7) compared to a non-cancer ductal organoid line. MAEA also demonstrated potential to discriminate early recurrence from late recurrence PDAC organoids. Our study suggests that identification of plasma protein biomarkers released by tumor cells may be feasible and of value to predict the clinical course of patients. Prediction of recurrence dynamics would help to stratify up-front resectable PDAC patients for neoadjuvant chemotherapy approaches in an individualized fashion. Here, MAEA and NT5E were the most promising candidates for further evaluation.
format	article
author	Marie-Claire Rittmann Saskia Hussung Lukas M. Braun Rhena F. U. Klar Esther A. Biesel Stefan Fichtner-Feigl Ralph Fritsch Uwe A. Wittel Dietrich A. Ruess
author_facet	Marie-Claire Rittmann Saskia Hussung Lukas M. Braun Rhena F. U. Klar Esther A. Biesel Stefan Fichtner-Feigl Ralph Fritsch Uwe A. Wittel Dietrich A. Ruess
author_sort	Marie-Claire Rittmann
title	Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma
title_short	Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma
title_full	Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma
title_fullStr	Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma
title_full_unstemmed	Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma
title_sort	plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eed841e9d8bb480f8aa6de85bb380eea
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_version_	1718378429024305152

Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma

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