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

作者：Rémy Nicolle, Cindy Canivet, Laurent Palazzo, Bertrand Napoléon, Mira Ayadi, Camille Pignolet, Jérôme Cros, Sophie Gourgou, Janick Sèlves, Jérôme Torrisani, Nelson Dusetti, Pierre Cordelier, Louis Buscail, Louis Buscail, Barbara Bournet, Barbara Bournet, Cindy Canivet, Louis Buscail, Louis Buscail, Nicolas Carrère, Fabrice Muscari, Bertrand Suc, Rosine Guimbaud, C. Couteau, Marion Deslandres, Pascale Rivera, Emily Alouany, Nadim Farés, Karl Barange, Janick Selves, Anne Gomez‐Brouchet, Adrian Culetto, Guillaume Le Cosquer, Marion Jaffrelot, Bertrand Napoléon, B. Pujol, Fabien Fumex, Jérôme Desrame, Christine Lefort, Vincent Lépilliez, Rodica Gincul, Pascal Artru, Léa Clavel, Anne‐Isabelle Lemaistre, Laurent Palazzo, Jérôme Cros, Sarah Tubiana, Nicolas Flori, Pierre Sénesse, Pierre‐Emmanuel Colombo, Emmanuelle Samalin-Scalzi, Fabienne Portalès, Sophie Gourgou, Lise Roca, Claire Honfo Ga, Carinne Plassot, Marc Ychou, Pierre Guibert, Christelle de la Fouchardière, Mathieu Sarabi, Patrice Peyrat, Séverine Tabone‐Eglinger, Caroline Renard, Guillaume Piessen, Stéphanie Truant, A Saudemont, Guillaume Y. Millet, Florence Renaud, Emmanuelle Leteurtre, Patrick Gelé, Eric Assénat, Jean-Michel Fabre, François-Régis Souche, Marie Dupuy, Anne-Marie Gorce-Dupuy, Jeanne Ramos, J. F. Seitz, Jean Hardwigsen, Emmanuelle Norguet-Monnereau, Philippe Grandval, Muriel Duluc, Dominique Figarella‐Branger, V. Vendrely, Clément Subtil, Eric Terrebonne, Jean-Frédéric Blanc, Jean‐Philippe Merlio, Dominique Farges-Bancel, Jean-Marc Gornet, Daniela Géromin, Geoffroy Vanbiervliet, Anne-Claire Frin, Delphine Ouvrier, Marie‐Christine Saint‐Paul, Philippe Berthelémy, Chelbabi Fouad, Stéphane Garcia, Nathalie Lesavre, Mohamed Gasmi, Marc Barthet, Vanessa Cottet, Cyrille Delpierre · 发表于：EBioMedicine · 年份：2024 · DOI：10.1016/j.ebiom.2024.105373 · 被引用次数：9 · 研究领域：Pancreatic and Hepatic Oncology Research、Cancer Genomics and Diagnostics、Gastric Cancer Management and Outcomes

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: Th...