title: Multidrug resistance-linked gene signature predicts overall survival of patients with primary ovarian serous carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 (log-rank 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gillet
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Calcagno
authors.forename: Sudhir
authors.initials: S
authors.lastname: Varma
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.forename: Mari
authors.initials: M
authors.lastname: Bunkholt Elstrand
authors.forename: Ram
authors.initials: R
authors.lastname: Ganapathi
authors.forename: Aparna A
authors.initials: AA
authors.lastname: Kamat
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Suresh V
authors.initials: SV
authors.lastname: Ambudkar
authors.forename: Michael V
authors.initials: MV
authors.lastname: Seiden
authors.forename: Bo R
authors.initials: BR
authors.lastname: Rueda
authors.forename: Michael M
authors.initials: MM
authors.lastname: Gottesman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D016190:Carboplatin / Q000008:administration & dosage; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D019450:Genes, MDR; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D016190:Carboplatin; D017239:Paclitaxel