Auteurs
[:en]Yuna Blum[:],
[:en]Pauline Duconseil[:],
[:en]Charles Vanbrugghe[:],
[:en]Nicolas Brandone[:],
[:en]Flora Poizat[:],
[:en]Julie Roques[:],
[:en]Martin Bigonnet[:],
[:en]Odile Gayet[:],
[:en]Marion Rubis[:],
[:en]Nabila Elarouci[:],
[:en]Lucile Armenoult[:],
[:en]Mira Ayadi[:],
[:en]Aurélien de Reyniès[:],
[:en]Marc Giovannini[:],
[:en]Philippe Grandval[:],
[:en]Stephane Garcia[:],
[:en]Cindy Canivet[:],
[:en]Barbara Bournet[:],
[:en]Louis Buscail[:],
[:en]BACAP Consortium[:],
[:en]Vincent Moutardier[:],
[:en]Marine Gilabert[:],
[:en]Juan Iovanna[:],
[:en]Nelson Dusetti[:],
[:en]
Abstract
Background
A significant gap in pancreatic ductal adenocarcinoma (PDAC) patient’s care is the lack of molecular parameters characterizing tumours and allowing a personalized treatment.
Methods
Patient-derived xenografts (PDX) were obtained from 76 consecutive PDAC and classified according to their histology into five groups. A PDAC molecular gradient (PAMG) was constructed from PDX transcriptomes recapitulating the five histological groups along a continuous gradient. The prognostic and predictive value for PMAG was evaluated in: i/ two independent series (n = 598) of resected tumours; ii/ 60 advanced tumours obtained by diagnostic EUS-guided biopsy needle flushing and iii/ on 28 biopsies from mFOLFIRINOX treated metastatic tumours.
Findings
A unique transcriptomic signature (PAGM) was generated with significant and independent prognostic value. PAMG significantly improves the characterization of PDAC heterogeneity compared to non-overlapping classifications as validated in 4 independent series of tumours (e.g. 308 consecutive resected PDAC, uHR=0.321 95% CI [0.207–0.5] and 60 locally-advanced or metastatic PDAC, uHR=0.308 95% CI [0.113–0.836]). The PAMG signature is also associated with progression under mFOLFIRINOX treatment (Pearson correlation to tumour response: -0.67, p-value < 0.001).
Interpretation
PAMG unify all PDAC pre-existing classifications inducing a shift in the actual paradigm of binary classifications towards a better characterization in a gradient.
Funding
Project funding was provided by INCa (Grants number 2018–078 and 2018–079, BACAP BCB INCa_6294), Canceropole PACA, DGOS (labellisation SIRIC), Amidex Foundation, Fondation de France, INSERM and Ligue Contre le Cancer.
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Autres publications
Date de publication :
09 Fév 2025Auteurs :
Hilmi Marc,
Flore Delecourt,
Raffenne Jérome,
Bourega Taib,
Nelson Dusetti,
Juan Iovanna,
Yuna Blum,
Magali Richard,
Cindy Neuzillet,
Couvelard Anne,
Matthieu Tihy,
De Mestier Louis,
Rebours Vinciane,
Nicolle Rémy,
Cros Jérome,
Date de publication :
02 Oct 2024Auteurs :
Yohann Loriot,
Maud Kamal,
Laurene Syx,
Nicolle Rémy,
Celia Dupain,
Naoual Mensourri,
Igor Duquesne,
Pernelle Lavaud,
Claudio Nicotra,
Maud Ngocamus,
Ludovic Lacroix,
Lambros Tselikas,
Gilles Crehange,
Luc Friboulet,
Zahra Castel-Ajgal,
Yann Neuzillet,
Edith Borcoman,
Philippe Beuzeboc,
Grégoire Marret,
Tom Gutman,
Jennifer Wong,
Francois Radvanyi,
Sylvain Dureau,
Jean-Yves Scoazec,
Nicolas Servant,
Yves Allory,
Benjamin Besse,
Fabrice Andre,
Christophe Le Tourneau,
Christophe Massard,
Ivan Bieche,
The immunological landscape in pancreatic ductal adenocarcinoma and overcoming resistance to immunotherapy
Lancet Gastroenterol Hepatol.
Date de publication :
29 Nov 2023Auteurs :
Hilmi Marc,
Matthieu Delaye,
Milena Muzzolini,
Nicolle Rémy,
Cros Jérome,
Hammel Pascal,
Victoire Cardot-Ruffino,
Cindy Neuzillet,
Date de publication :
12 Nov 2023Auteurs :
Nicolle Rémy,
Jean-Baptiste Bachet,
Alexandre Harlé,
Juan Iovanna,
Hammel Pascal,
Rebours Vinciane,
Anthony Turpin,
Meher Ben Abdelghani,
Alice Wei,
Emmanuel Mitry,
Anthony Lopez,
James Biagi,
Eric François,
Pascal Artru,
Aurélien Lambert,
Daniel J Renouf,
Laure Monard,
Marjorie Mauduit,
Nelson Dusetti,
Thierry Conroy,
Cros Jérome,