title: Transcriptomic analysis predicts survival and sensitivity to anticancer drugs of patients with a pancreatic adenocarcinoma.
abstract: A major impediment to the effective treatment of patients with pancreatic ductal adenocarcinoma (PDAC) is the molecular heterogeneity of this disease, which is reflected in an equally diverse pattern of clinical outcome and in responses to therapies. We developed an efficient strategy in which PDAC samples from 17 consecutive patients were collected by endoscopic ultrasound-guided fine-needle aspiration or surgery and were preserved as breathing tumors by xenografting and as a primary culture of epithelial cells. Transcriptomic analysis was performed from breathing tumors by an Affymetrix approach. We observed significant heterogeneity in the RNA expression profile of tumors. However, the bioinformatic analysis of these data was able to discriminate between patients with long- and short-term survival corresponding to patients with moderately or poorly differentiated PDAC tumors, respectively. Primary culture of cells allowed us to analyze their relative sensitivity to anticancer drugs in vitro using a chemogram, similar to the antibiogram for microorganisms, establishing an individual profile of drug sensitivity. As expected, the response was patient dependent. We also found that transcriptomic analysis predicts the sensitivity of cells to the five anticancer drugs most frequently used to treat patients with PDAC. In conclusion, using this approach, we found that transcriptomic analysis could predict the sensitivity to anticancer drugs and the clinical outcome of patients with PDAC.
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Duconseil
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Gilabert
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Gayet
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Loncle
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France; Department of Surgery, Hôpital Nord, Marseille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Moutardier
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France; Paoli-Calmettes Institute, Marseille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Turrini
authors.affiliation: Genomic Center, CHUL Research Centre, Quebec City, Quebec, Canada.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Paoli-Calmettes Institute, Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Ewald
authors.affiliation: Paoli-Calmettes Institute, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Giovannini
authors.affiliation: Department of Gastroenterology, Hôpital Nord, Marseille, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Gasmi
authors.affiliation: Paoli-Calmettes Institute, Marseille, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bories
authors.affiliation: Department of Gastroenterology, Hôpital Nord, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Barthet
authors.affiliation: Department of Surgery, La Timone Hospital, Marseille, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ouaissi
authors.affiliation: Paoli-Calmettes Institute, Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Goncalves
authors.affiliation: Paoli-Calmettes Institute, Marseille, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Poizat
authors.affiliation: Paoli-Calmettes Institute, Marseille, France.
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Raoul
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France; Department of Surgery, Hôpital Nord, Marseille, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Secq
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France; Department of Surgery, Hôpital Nord, Marseille, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Garcia
authors.affiliation: Paoli-Calmettes Institute, Marseille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France. Electronic address: juan.iovanna@inserm.fr.
authors.forename: Juan
authors.initials: J
authors.lastname: Iovanna
authors.affiliation: Cancer Research Center of Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Scientific and Technological Park of Luminy, Marseille, France. Electronic address: nelson.dusetti@inserm.fr.
authors.forename: Nelson
authors.initials: N
authors.lastname: Dusetti
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D044963:Biopsy, Fine-Needle; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004724:Endoscopy; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling; D016019:Survival Analysis; D059467:Transcriptome / Q000235:genetics; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger