Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer.

Chowdhury, Shrabanti; Kennedy, Jacob J; Ivey, Richard G; Murillo, Oscar D; Hosseini, Noshad; Song, Xiaoyu; Petralia, Francesca; Calinawan, Anna et al. · Cell · 2023

retrospective_cohort · Level III

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Abstract

To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.

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