Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer.
retrospective_cohort · Level III
Where this comes from
- Record sourced from PubMed, PMID 37541199.
- Also identified by DOI 10.1016/j.cell.2023.07.004 and PMC identifier 10414761.
- Licence recorded as CC BY-NC-ND.
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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.
Medical subject headings
- Cystadenocarcinoma, Serous
- Ovarian Neoplasms
- Proteogenomics