Multi-gene expression predictors of single drug responses to adjuvant chemotherapy in ovarian carcinoma: predicting platinum resistance.
GSE30161_eset.RdDespite advances in radical surgery and chemotherapy delivery, ovarian cancer is the most lethal gynecologic malignancy. Standard therapy includes treatment with platinum-based combination chemotherapies yet there is no biomarker model to predict their responses to these agents. We here have developed and independently tested our multi-gene molecular predictors for forecasting patients' responses to individual drugs on a cohort of 55 ovarian cancer patients. To independently validate these molecular predictors, we performed microarray profiling on FFPE tumor samples of 55 ovarian cancer patients (UVA-55) treated with platinum-based adjuvant chemotherapy. Genome-wide chemosensitivity biomarkers were initially discovered from the in vitro drug activities and genomic expression data for carboplatin and paclitaxel, respectively. Multivariate predictors were trained with the cell line data and then evaluated with a historical patient cohort. For the UVA-55 cohort, the carboplatin, taxol, and combination predictors significantly stratified responder patients and non-responder patients (p = 0.019, 0.04, 0.014) with sensitivity = 91%, 96%, 93 and NPV = 57%, 67%, 67% in pathologic clinical response. The combination predictor also demonstrated a significant survival difference between predicted responders and non-responders with a median survival of 55.4 months vs. 32.1 months. Thus, COXEN single- and combination-drug predictors successfully stratified platinum resistance and taxane response in an independent cohort of ovarian cancer patients based on their FFPE tumor samples.
Usage
data( GSE30161_eset )Format
experimentData(eset):
Experiment data
Experimenter name: Ferriss JS, Kim Y, Duska L, Birrer M, Levine DA, Moskaluk C,Theodorescu D, Lee JK
Laboratory: Ferriss, Lee 2012
Contact information:
Title: Multi-gene expression predictors of single drug responses to adjuvant chemotherapy in ovarian carcinoma: predicting platinum resistance.
URL:
PMIDs: 22348014
Abstract: A 215 word abstract is available. Use 'abstract' method.
Information is available on: preprocessing
notes:
platform_title:
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
platform_shorttitle:
Affymetrix HG-U133Plus2
platform_summary:
hgu133plus2
platform_manufacturer:
Affymetrix
platform_distribution:
commercial
platform_accession:
GPL570
platform_technology:
in situ oligonucleotide
Preprocessing: frma
featureData(eset):
An object of class 'AnnotatedDataFrame'
featureNames: A1BG A1BG-AS1 ... ZZZ3 (19816 total)
varLabels: probeset gene
varMetadata: labelDescription
Details
assayData: 19816 features, 58 samples
Platform type: hgu133plus2
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
58.00 58.00 58.00 36.00 4.19 2.70 6.17
---------------------------
Available sample meta-data:
---------------------------
alt_sample_name:
Length Class Mode
58 character character
sample_type:
tumor
58
histological_type:
Length Class Mode
58 character character
summarygrade:
high low NA's
33 21 4
summarystage:
late
58
tumorstage:
3 4
53 5
substage:
a b c
9 11 38
grade:
1 2 3 NA's
2 19 33 4
age_at_initial_pathologic_diagnosis:
Min. 1st Qu. Median Mean 3rd Qu. Max.
38.00 53.50 62.00 62.57 72.00 85.00
pltx:
y
58
tax:
n y
4 54
neo:
n
58
days_to_tumor_recurrence:
Min. 1st Qu. Median Mean 3rd Qu. Max.
12.0 255.2 386.0 742.1 768.2 4208.0
recurrence_status:
norecurrence recurrence NA's
6 48 4
days_to_death:
Min. 1st Qu. Median Mean 3rd Qu. Max.
49.0 585.2 1010.0 1375.0 2131.0 4208.0
vital_status:
deceased living
36 22
debulking:
optimal suboptimal NA's
26 30 2
batch:
2009-10-07 2009-10-08 2009-10-09 2009-10-20
28 18 8 4
uncurated_author_metadata:
Length Class Mode
58 character character