Implementing an online tool for genomewide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients

B. Györffy, András Lánczky, Zoltán Szállási

Research output: Contribution to journalArticle

350 Citations (Scopus)

Abstract

The validation of prognostic biomarkers in large independent patient cohorts is a major bottleneck in ovarian cancer research. We implemented an online tool to assess the prognostic value of the expression levels of all microarray-quantified genes in ovarian cancer patients. First, a database was set up using gene expression data and survival information of 1287 ovarian cancer patients downloaded from Gene Expression Omnibus and The Cancer Genome Atlas (Affymetrix HG-U133A, HG-U133A 2.0, and HG-U133 Plus 2.0 microarrays). After quality control and normalization, only probes present on all three Affymetrix platforms were retained (n=22 277). To analyze the prognostic value of the selected gene, we divided the patients into two groups according to various quantile expressions of the gene. These groups were then compared using progression-free survival (n=1090) or overall survival (n=1287). A Kaplan-Meier survival plot was generated and significance was computed. The tool can be accessed online at www.kmplot.com/ovar. We used this integrative data analysis tool to validate the prognostic power of 37 biomarkers identified in the literature. Of these, CA125 (MUC16; P=3.7×10 -5, hazard ratio (HR)=1.4), CDKN1B (P=5.4×10 -5, HR=1.4), KLK6 (P=0.002, HR=0.79), IFNG (P=0.004, HR=0.81), P16 (P=0.02, HR=0.66), and BIRC5 (P=0.00017, HR=0.75) were associated with survival. The combination of several probe sets can further increase prediction efficiency. In summary, we developed a global online biomarker validation platform that mines all available microarray data to assess the prognostic power of 22 277 genes in 1287 ovarian cancer patients. We specifically used this tool to evaluate the effect of 37 previously published biomarkers on ovarian cancer prognosis.

Original languageEnglish
Pages (from-to)197-208
Number of pages12
JournalEndocrine-Related Cancer
Volume19
Issue number2
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Ovarian Neoplasms
Biomarkers
Survival
Gene Expression
Genes
Atlases
Quality Control
Disease-Free Survival
Genome
Databases
Research
Neoplasms

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Implementing an online tool for genomewide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients. / Györffy, B.; Lánczky, András; Szállási, Zoltán.

In: Endocrine-Related Cancer, Vol. 19, No. 2, 04.2012, p. 197-208.

Research output: Contribution to journalArticle

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