Single-sample expression-based chemo-sensitivity score improves survival associations independently from genomic...

Platinum-based chemotherapies are first-line treatments for ovarian cancer (OC) patients. Although chemotherapy has a high initial response rate, some patients exhibit inherent chemo-resistance. With advancements of molecular and genomic profiling, it is of high interest to identify molecular and genomic signatures predictive of chemo- sensitivity priori to treatment initiation in order to better personalize care decisions. Previous efforts have made use of mRNA expression levels of selected genes responsible for repairing DNA damage, under the hypothesis that chemo efficacy is associated with their proficiency. However, the resulting scores have been difficult to interpret. In this study, we designed a single-sample based approach known as eCARD to investigate chemo-sensitivity in ovarian cancer patients from The Cancer Genome Atlas. We demonstrated that the proposed single-sample based approach can lead to a molecular-based chemo-sensitivity score predictive of prognosis, which validates in 5 independent cohorts, and associates with increasing mutation burden and likelihood of BRCA1/2 mutation.