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

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: 10.13039/501100006364Institut National Du Cancer (BCB INCa_7294), 10.13039/501100015613CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

Authors

Institutions

Publication Details

Journal
EBioMedicine
Published
2024-10-08
DOI
https://doi.org/10.1016/j.ebiom.2024.105373
Citations
8
Primary Topic
Pancreatic and Hepatic Oncology Research
Type
article
Field-Weighted Citation Impact
2.26

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Dominique Figarella‐Branger, A Saudemont, Nelson Dusetti, Mira Ayadi et al.
8 citations
EBioMedicine
Pancreatic and Hepatic Oncology Research
2.26
article

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

Dominique Figarella‐Branger, A Saudemont, Nelson Dusetti, Mira Ayadi, Marc Barthet, Cyrille Delpierre, Nadim Farés, Adrian Culetto, Pascal Artru, Karl Barange, Janick Sèlves, Philippe Berthelémy, Marc Ychou, Vanessa Cottet, Philippe Grandval, Guillaume Piessen, Emmanuelle Norguet-Monnereau, Daniela Géromin, Delphine Ouvrier, Marion Deslandres, Matthieu Sarabi, Rosine Guimbaud, Fabrice Muscari, Guillaume Le Cosquer, Bertrand Napoléon, Emmanuelle Samalin-Scalzi, Anne-Marie Gorce-Dupuy, Jérôme Torrisani, Mohamed Gasmi, Rémy Nicolle, Anne Gomez‐Brouchet, Pierre Sénesse, Pierre‐Emmanuel Colombo, Eric Terrebonne, V. Vendrely, Bertrand Suc, Eric Assénat, Marion Jaffrelot, Caroline Renard, Marie Dupuy, Clément Subtil, Séverine Tabone‐Eglinger, Sophie Gourgou, Emmanuelle Leteurtre, C. Couteau, Patrick Gelé, Florence Renaud, José Ramos, Jérôme Cros, Christelle de la Fouchardière, Fabien Fumex, B. Pujol, Rodica Gincul, Fabienne Portalès, Muriel Duluc, Barbara Bournet, Sarah Tubiana, Stéphanie Truant, Jean Hardwigsen, Jérôme Desrame, Geoffroy Vanbiervliet, Jean‐Philippe Merlio, Guillaume Y. Millet, Louis Buscail, Pierre Cordelier, Vincent Lépilliez, Anne‐Isabelle Lemaistre, Nicolas Flori, Régis Souche, Léa Clavel, Patrice Peyrat, Cindy Canivet, Nathalie Lesavre, Camille Pignolet, Dominique Farges-Bancel, Jean-Michel Fabre, Stéphane Garcia, Jean-Frédéric Blanc, Carine Plassot, Laurent Palazzo, Marie‐Christine Saint‐Paul, Nicolas Carrère, Pascale Rivera, Anne-Claire Frin, Lise Roca, Pierre Guibert, Christine Lefort, J. F. Seitz, Jean-Marc Gornet, Claire Honfo Ga, Chelbabi Fouad, Emily Alouany
article en
8 citations

Abstract

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: 10.13039/501100006364Institut National Du Cancer (BCB INCa_7294), 10.13039/501100015613CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

EBioMedicineVol. 109
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Cité (FR), Hôpital Beaujon (FR), Centre Hospitalier Universitaire de Toulouse (FR), Centre de Recherches en Cancérologie de Toulouse (FR), Sorbonne Paris Cité (FR), La Ligue Contre le Cancer (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Clinique du Sport (FR), Hôpital Rangueil (FR), Hôpital Privé Jean Mermo (FR), Centre de Recherche sur l'Inflammation (FR), Institut de Recherche en Cancérologie de Montpellier (FR), Centre de Recherche en Cancérologie de Marseille (FR), Clinique Ambroise Paré (FR), Générale de Santé (FR)
Institut National de la Santé et de la Recherche Médicale, Institut National Du Cancer
Zero hunger
Openalex Percentile: Top 10%
Pancreatic and Hepatic Oncology Research
2.26
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.