Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features
Pancreatic ducal adenocarcinoma is classically diagnosed in the 7th decade, but approximately 10% of patients are diagnosed under 55 years (y.o.). While the genomic and transcriptomic landscapes of late-onset tumors (LOT) have been described, little is known about early-onset tumors (EOT). Ageing is...
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2021-03-01
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doaj-d44b3a55f4984cff89dd4e0f23b67d462021-03-12T00:05:09ZengMDPI AGCancers2072-66942021-03-01131234123410.3390/cancers13061234Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular FeaturesJérôme Raffenne0Fernando A. Martin1Rémy Nicolle2Marina Konta3Yuna Blum4Jérôme Torrisani5Francesco Puleo6Jean Baptiste Bachet7Magali Svrcek8Armel Bardier-Dupas9Jean Francois Emile10Peter Demetter11Miroslav Radman12Jean Luc Van Laethem13Pascal Hammel14Vinciane Rebours15Valérie Paradis16Anne Couvelard17Jérôme Cros18INSERM U1149, Inflammation Research Center, Beaujon Hospital, 92110 Clichy, FranceINSERM U1149, Inflammation Research Center, Beaujon Hospital, 92110 Clichy, FranceProgramme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, FranceProteomic Research Group, Mediterranean Institute for Life Science, 21000 Split, CroatiaProgramme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, FranceInstitut National de la Santé et de la Recherche Médicale, INSERM Unit 1037, Centre de Recherches en Cancérologie de Toulouse, CEDEX 1, 31 037 Toulouse, FranceDepartment of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, BelgiumDepartment of Gastroenterology, Pitié-Salpetriére Hospital, Sorbonne Universités, UPMC Université, 75013 Paris, FranceDepartment of Pathology, Saint Antoine Hospital, 75012 Paris, FranceDepartment of Pathology, Pitié-Salpetriére Hospital, 75013 Paris, FranceDepartment of Pathology, Ambroise Paré Hospital, 92100 Boulogne-Billancourt, FranceDepartment of Pathology, Erasme Hospital, 1000 Brussels, BelgiumProteomic Research Group, Mediterranean Institute for Life Science, 21000 Split, CroatiaLaboratory of Experimental Gastroenterology and Department of Gastroenterology and Digestive Oncology, Hopital Erasme, Université Libre de Bruxelles, 1070 Brussels, BelgiumINSERM U1149, Inflammation Research Center, Beaujon Hospital, 92110 Clichy, FranceINSERM U1149, Inflammation Research Center, Beaujon Hospital, 92110 Clichy, FranceINSERM U1149, Inflammation Research Center, Beaujon Hospital, 92110 Clichy, FranceINSERM U1149, Inflammation Research Center, Beaujon Hospital, 92110 Clichy, FranceINSERM U1149, Inflammation Research Center, Beaujon Hospital, 92110 Clichy, FrancePancreatic ducal adenocarcinoma is classically diagnosed in the 7th decade, but approximately 10% of patients are diagnosed under 55 years (y.o.). While the genomic and transcriptomic landscapes of late-onset tumors (LOT) have been described, little is known about early-onset tumors (EOT). Ageing is known to impact DNA methylation and proteome integrity through carbonylation-related oxidative damages. We therefore aimed to assess the global molecular features of EOT. We compared 176 EOT (≤55 y.o.) and 316 LOT (≥70 y.o.) from three distinct surgical cohorts at the clinical/genomic/epigenomic/transcriptomic level. Furthermore, we assessed oxidative stress responses and oxidative proteome damages using 2D gel electrophoresis followed by mass spectrometry protein identification. There was no consistent clinical difference between EOT and LOT across the three cohorts. The mutational landscape of key driver genes and the global methylation profile were similar in the two groups. LOT did display age-related features such as enriched DNA repair gene signatures and upregulation of oxidative stress defenses together with increased proteome carbonylation. However, these age-related differences were more preeminent in non-tumor tissues while tumor proteome and proteome damages were fairly comparable. In conclusion, this multi-omics comparison showed that EOT harbor a comparable molecular profile to that of LOT.https://www.mdpi.com/2072-6694/13/6/1234PDACyoung patientselderly patientsmulti-omics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jérôme Raffenne Fernando A. Martin Rémy Nicolle Marina Konta Yuna Blum Jérôme Torrisani Francesco Puleo Jean Baptiste Bachet Magali Svrcek Armel Bardier-Dupas Jean Francois Emile Peter Demetter Miroslav Radman Jean Luc Van Laethem Pascal Hammel Vinciane Rebours Valérie Paradis Anne Couvelard Jérôme Cros |
spellingShingle |
Jérôme Raffenne Fernando A. Martin Rémy Nicolle Marina Konta Yuna Blum Jérôme Torrisani Francesco Puleo Jean Baptiste Bachet Magali Svrcek Armel Bardier-Dupas Jean Francois Emile Peter Demetter Miroslav Radman Jean Luc Van Laethem Pascal Hammel Vinciane Rebours Valérie Paradis Anne Couvelard Jérôme Cros Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features Cancers PDAC young patients elderly patients multi-omics |
author_facet |
Jérôme Raffenne Fernando A. Martin Rémy Nicolle Marina Konta Yuna Blum Jérôme Torrisani Francesco Puleo Jean Baptiste Bachet Magali Svrcek Armel Bardier-Dupas Jean Francois Emile Peter Demetter Miroslav Radman Jean Luc Van Laethem Pascal Hammel Vinciane Rebours Valérie Paradis Anne Couvelard Jérôme Cros |
author_sort |
Jérôme Raffenne |
title |
Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features |
title_short |
Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features |
title_full |
Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features |
title_fullStr |
Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features |
title_full_unstemmed |
Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features |
title_sort |
pancreatic ductal adenocarcinoma arising in young and old patients displays similar molecular features |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-03-01 |
description |
Pancreatic ducal adenocarcinoma is classically diagnosed in the 7th decade, but approximately 10% of patients are diagnosed under 55 years (y.o.). While the genomic and transcriptomic landscapes of late-onset tumors (LOT) have been described, little is known about early-onset tumors (EOT). Ageing is known to impact DNA methylation and proteome integrity through carbonylation-related oxidative damages. We therefore aimed to assess the global molecular features of EOT. We compared 176 EOT (≤55 y.o.) and 316 LOT (≥70 y.o.) from three distinct surgical cohorts at the clinical/genomic/epigenomic/transcriptomic level. Furthermore, we assessed oxidative stress responses and oxidative proteome damages using 2D gel electrophoresis followed by mass spectrometry protein identification. There was no consistent clinical difference between EOT and LOT across the three cohorts. The mutational landscape of key driver genes and the global methylation profile were similar in the two groups. LOT did display age-related features such as enriched DNA repair gene signatures and upregulation of oxidative stress defenses together with increased proteome carbonylation. However, these age-related differences were more preeminent in non-tumor tissues while tumor proteome and proteome damages were fairly comparable. In conclusion, this multi-omics comparison showed that EOT harbor a comparable molecular profile to that of LOT. |
topic |
PDAC young patients elderly patients multi-omics |
url |
https://www.mdpi.com/2072-6694/13/6/1234 |
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