Multidrug resistance-linked gene signature predicts overall survival of patients with primary ovarian serous carcinoma

J.-P. Gillet, A.M. Calcagno, S. Varma, B. Davidson, M.B. Elstrand, R. Ganapathi, A.A. Kamat, A.K. Sood, S.V. Ambudkar, M.V. Seiden, B.R. Rueda, M.M. Gottesman

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Résumé

Purpose: This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. Experimental Design: We applied a customized TaqMan low density array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes. Results: Leave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (OS; P = 0.06), four covariates (age, stage, CA125 level, and surgical debulking) do (P=0.03). When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in OS prediction (logrank statistic P <0.003). The predictive power of this 11-gene signature was confirmed by dividing high- and low-risk patient groups, as defined by their clinical covariates, into four specific risk groups on the basis of expression levels. Conclusion: This study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin- and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer.
langue originaleAnglais
Pages (de - à)3197-3206
Nombre de pages10
journalClinical Cancer Research
Volume18
Numéro de publication11
Les DOIs
Etat de la publicationPublié - 1 juin 2012

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