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

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.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.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.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.

Usage

data( GSE30009_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Gillet JP, Calcagno AM, Varma S, Davidson B et al. Multidrug resistance-linked gene signature predicts overall survival of patients with primary ovarian serous carcinoma. Clin Cancer Res 2012 Jun 1;18(11):3197-206.
  Laboratory: Gillet, Gottesman 2012
  Contact information:
  Title: Multidrug resistance-linked gene signature predicts overall survival of patients with primary ovarian serous carcinoma.
  URL:
  PMIDs: 22492981

  Abstract: A 244 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing
  notes:
   platform_title:
      TaqMan qRT-PCR Homo sapiens Low-Density Array 380
   platform_shorttitle:
      TaqMan qRT-PCR
   platform_summary:
      NA
   platform_manufacturer:
      TaqMan
   platform_distribution:
      custom
   platform_accession:
      GPL13728
   platform_technology:
      qRT-PCR

Preprocessing: default
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: ABCA1 ABCA10 ... XRCC6 (359 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 359 features, 103 samples
Platform type: NA
Overall survival time-to-event summary (in years):
Call: survfit(formula = Surv(time, cens) ~ -1)

records   n.max n.start  events  median 0.95LCL 0.95UCL
 103.00  103.00  103.00   57.00    3.42    2.92    5.34

---------------------------
Available sample meta-data:
---------------------------

alt_sample_name:
   Length     Class      Mode
      103 character character

sample_type:
borderline      tumor
         1        102

histological_type:
clearcell       ser
        1       102

summarygrade:
high  low NA's
  92    9    2

summarystage:
late
 103

tumorstage:
 3  4
82 21

substage:
   b    c NA's
   2   60   41

grade:
   1    2    3 NA's
   4    5   92    2

age_at_initial_pathologic_diagnosis:
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.
  30.00   56.00   61.00   62.45   71.50   87.00

days_to_death:
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.
     24     598    1053    1156    1568    4748

vital_status:
deceased   living
      57       46

debulking:
   optimal suboptimal
        81         22

uncurated_author_metadata:
   Length     Class      Mode
      103 character character