abstract: Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients.

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 1,287 ovarian cancer patients downloaded from GEO and TCGA (Affymetrix HGU133A, HGU133A 2.0 and HGU133+2 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, the patients are divided into two groups according to various quantile expressions of the gene. These groups are then compared using progression free survival (n=1,090) or overall survival (n=1,287). A Kaplan-Meier survival plot is generated and significance is 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 (p=3.7e-5, HR=1.4), CDKN1B (p=5.4e-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 1,287 ovarian cancer patients.

We specifically used this tool to evaluate the effect of 37 previously published biomarkers on ovarian cancer prognosis."