IPI59: An Actionable Biomarker to Improve Treatment Response in Serous Ovarian Carcinoma Patients
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Despite improvements in operative management and therapies, overall survival rates in advanced ovarian cancer have remained largely unchanged over the past three decades. Although it is possible to identify high-risk patients following surgery, the knowledge does not provide information about the genomic aberrations conferring risk, or the implications for treatment. To address these challenges, we developed an integrative pathway-index model and applied it to messenger RNA expression from 458 patients with serous ovarian carcinoma from the Cancer Genome Atlas project. The biomarker derived from this approach, IPI59, contains 59 genes from six pathways. As we demonstrate using independent datasets from six studies, IPI59 is strongly associated with overall and progression-free survival, and also identifies high-risk patients who may benefit from enhanced adjuvant therapy.
KeywordsAdjuvant Therapy Ovarian Cancer Patient Serous Ovarian Carcinoma Affymetrix Human Genome Lasso Regression
The authors thank Drs. Michael Newton and Ning Leng for suggestions that improved the manuscript. This research was supported by NIH GM102756, NIH U54 AI117924, NIH K01LM012100, and the Clinical and Translational Science Institute of Southeastern Wisconsin (NIH UL1RR031973). Results were generated in part using data from the Cancer Genome Atlas (TCGA) pilot project established by the NCI and NHGRI. Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov/.
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