Transcriptomics

Dataset Information

12

Transcriptome Analysis Predicts Clinical Outcome and Sensitivity to Anticancer Drugs of patients with a Pancreatic Adenocarcinoma


ABSTRACT: A major impediment to the effective treatment of patients with PDAC (Pancreatic Ductal Adenocarcinoma) is the molecular heterogeneity of the disease, which is reflected in an equally diverse pattern of clinical responses to therapy. We developed an efficient strategy in which PDAC samples from 17 consecutively patients were obtained by EUS-FNA or surgery, their cells maintained as a primary culture and tumors as breathing tumors by xenografting in immunosuppressed mice. For these patients a clinical follow up was obtained. On the breathing tumors we studied the RNA expression profile by an Affymetrix approach. We observed a significant heterogeneity in their RNA expression profile, however, the transcriptome was able to discriminate patients with long- or short-time survival which correspond to moderately- or poorly-differentiated PDAC tumors respectively. Cells allowed us the possibility to analyze their relative sensitivity to several anticancer drugs in vitro by developing a chimiogram, like an antibiogram for microorganisms, with several anticancer drugs for obtaining an individual profile of drug sensitivity and as expected, the response was patient-dependent. Interestingly, using this approach, we also found that the transcriptome analysis could predict the sensitivity to some anticancer drugs of patients with a PDAC. In conclusion, using this approach, we found that the transcriptome analysis could predict the sensitivity to some anticancer drugs and the clinical outcome of patients with a PDAC. PDAC samples from 17 consecutively patients were obtained by Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) or surgery. Consents of informed patients were collected, and the ethics review board of the three centers approved the study. All samples were anonymized and obtained in accordance with institutional review boards. EUS-FNA cells were maintained as a primary culture and tumors as breathing tumors by xenografting in immunosuppressed mice. We characterized 17 PDAC-derived xenografts by duplicate. Total RNA was extracted and hybridized on Human Gene 2.0 (Genechip, Affymetrix) as described previously (Hamidi et al. JCI 122: 2092-2103, 2012).

ORGANISM(S): Homo sapiens  

SUBMITTER: Mohamed Gasmi   Odile Gayet  Pauline Duconseil  Marc Giovannini  Stephane Garcia  Marine Gilabert  Nelson Dusetti  Patrice Viens  Ezequiel L Calvo  Anthony Goncalves  Jacques Ewald  Vincent Moutardier  Olivier Turrini  Juan Iovanna  Ezequiel Calvo  Jean Raoul  Mehdi Ouaissi  Celine Loncle  Veronique Secq  Marc Barthet  Erwan Bories 

PROVIDER: E-GEOD-55513 | ArrayExpress | 2015-04-09

SECONDARY ACCESSION(S): GSE55513PRJNA239817

REPOSITORIES: GEO, ArrayExpress

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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  ...[more]

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