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Proteogenomic analysis of chemo-refractory high grade serous ovarian cancer

ABSTRACT: To improve our understanding of the molecular basis 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 independent validation cohorts (spanning four academic centers) and utilizing two biospecimen types (formalin-fixed paraffin-embedded and frozen tumor biopsies). As the largest and most comprehensive study of refractory ovarian cancers to date, this effort identified a 64-protein signature that predicts a subset of HGSOCs refractory to initial platinum-based therapy with high specificity and is validated in two independent patient cohorts. We also detected significant association between lack of Ch17 loss-of-heterozygosity and refractory disease. Moreover, based on protein pathway expression, five novel clusters of HGSOC were identified and validated across two independent patient cohorts, as well as in patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic targets.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jacob Kennedy

PROVIDER: PXD040742 | panorama | Mon Sep 18 00:00:00 BST 2023

REPOSITORIES: PanoramaPublic

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

Chowdhury Shrabanti S Kennedy Jacob J JJ Ivey Richard G RG Murillo Oscar D OD Hosseini Noshad N Song Xiaoyu X Petralia Francesca F Calinawan Anna A Savage Sara R SR Berry Anna B AB Reva Boris B Ozbek Umut U Krek Azra A Ma Weiping W da Veiga Leprevost Felipe F Ji Jiayi J Yoo Seungyeul S Lin Chenwei C Voytovich Uliana J UJ Huang Yajue Y Lee Sun-Hee SH Bergan Lindsay L Lorentzen Travis D TD Mesri Mehdi M Rodriguez Henry H Hoofnagle Andrew N AN Herbert Zachary T ZT Nesvizhskii Alexey I AI Zhang Bing B Whiteaker Jeffrey R JR Fenyo David D McKerrow Wilson W Wang Joshua J Schürer Stephan C SC Stathias Vasileios V Chen X Steven XS Barcellos-Hoff Mary Helen MH Starr Timothy K TK Winterhoff Boris J BJ Nelson Andrew C AC Mok Samuel C SC Kaufmann Scott H SH Drescher Charles C Cieslik Marcin M Wang Pei P Birrer Michael J MJ Paulovich Amanda G AG

Cell 20230801 16

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. ...[more]

PMID: 37541199

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Dataset Information

Proteogenomic analysis of chemo-refractory high grade serous ovarian cancer

Publications

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

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