Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre study.

Autor:	Nicolle R; Université Paris Cité, Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris F-75018, France., Canivet C; Service de Gastroentérologie et Pancréatologie, Centre Hospitalier Universitaire de Toulouse-Rangueil (CHU), Toulouse, France., Palazzo L; Service d'Endoscopie, Clinique du Trocadéro, Paris, France., Napoléon B; Service de Gastroentérologie, Hôpital Privé Jean Mermoz, Ramsay Générale de Santé, Lyon, France., Ayadi M; Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre Le Cancer, Paris, France., Pignolet C; Université Paris Cité, Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris F-75018, France., Cros J; Université Paris Cité, Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris F-75018, France; Université Paris Cité, Service d'Anatomopathologie, Centre Hospitalier Universitaire Beaujon/Bichat (APHP), Clichy/Paris, France., Gourgou S; Institut du Cancer de Montpellier-Val d'Aurelle, Université de Montpellier, Montpellier, France., Selves J; Service d'Anatomopathologie, Institut Universitaire du Cancer-Oncopole de Toulouse, Centre Hospitalier Universitaire (CHU), Toulouse, France., Torrisani J; Centre de Recherches en Cancérologie de Toulouse, Inserm U1037, CRCT, Université de Toulouse, Inserm, CNRS, Toulouse, France., Dusetti N; Centre de Recherche sur le Cancer de Marseille, Inserm, CNRS, Institut Paoli-Calmettes, Université Aix-Marseille, Marseille, France., Cordelier P; Centre de Recherches en Cancérologie de Toulouse, Inserm U1037, CRCT, Université de Toulouse, Inserm, CNRS, Toulouse, France., Buscail L; Service de Gastroentérologie et Pancréatologie, Centre Hospitalier Universitaire de Toulouse-Rangueil (CHU), Toulouse, France; Centre de Recherches en Cancérologie de Toulouse, Inserm U1037, CRCT, Université de Toulouse, Inserm, CNRS, Toulouse, France. Electronic address: buscail.l@chu-toulouse.fr., Bournet B; Service de Gastroentérologie et Pancréatologie, Centre Hospitalier Universitaire de Toulouse-Rangueil (CHU), Toulouse, France; Centre de Recherches en Cancérologie de Toulouse, Inserm U1037, CRCT, Université de Toulouse, Inserm, CNRS, Toulouse, France.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2024 Nov; Vol. 109, pp. 105373. Date of Electronic Publication: 2024 Oct 08.
DOI:	10.1016/j.ebiom.2024.105373
Abstrakt:	Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program). Competing Interests: Declaration of interests Nelson Dusetti is co-owner and inventor for the patent (PCT/EP2022/065222.462) dedicated to predictive medicine for pancreatic cancer. None of the other authors has competing interest in relation to the present work. Investigators implicated in the BACAP consortia received a financial compensation for patient inclusion and data collection from Toulouse Hospital as the sponsor of BACAP cohort funded by a grant from INCa. (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu