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

Jean Pierre Gillet, Anna Maria Calcagno, Sudhir Varma, Ben Davidson, Mari Bunkholt Elstrand, Ram Ganapathi, Aparna A. Kamat, Anil K. Sood, Suresh V. Ambudkar, Michael V. Seiden, Bo R. Rueda, Michael M. Gottesman

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3197-3206
Number of pages10
JournalClinical Cancer Research
Volume18
Issue number11
DOIs
StatePublished - Jun 1 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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