Details

Autor(en) / Beteiligte

• Chowdhury, Shrabanti
• Kennedy, Jacob J.
• Ivey, Richard G.
• Murillo, Oscar D.
• Hosseini, Noshad
• Song, Xiaoyu
• Petralia, Francesca
• Calinawan, Anna
• Savage, Sara R.
• Berry, Anna B.
• Reva, Boris
• Ozbek, Umut
• Krek, Azra
• Ma, Weiping
• da Veiga Leprevost, Felipe
• Ji, Jiayi
• Yoo, Seungyeul
• Lin, Chenwei
• Voytovich, Uliana J.
• Huang, Yajue
• Lee, Sun-Hee
• Bergan, Lindsay
• Lorentzen, Travis D.
• Mesri, Mehdi
• Rodriguez, Henry
• Hoofnagle, Andrew N.
• Herbert, Zachary T.
• Nesvizhskii, Alexey I.
• Zhang, Bing
• Whiteaker, Jeffrey R.
• Fenyo, David
• McKerrow, Wilson
• Wang, Joshua
• Schürer, Stephan C.
• Stathias, Vasileios
• Chen, X. Steven
• Barcellos-Hoff, Mary Helen
• Starr, Timothy K.
• Winterhoff, Boris J.
• Nelson, Andrew C.
• Mok, Samuel C.
• Kaufmann, Scott H.
• Drescher, Charles
• Cieslik, Marcin
• Wang, Pei
• Birrer, Michael J.
• Paulovich, Amanda G.

Titel

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

Ist Teil von

• Cell, 2023-08, Vol.186 (16), p.3476-3498.e35

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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. [Display omitted] •A comprehensive proteogenomic analysis of 242 HGSOC tumors was performed•A lack of Chr17-LOH was observed to be associated with refractoriness•A 64-protein signature predicts refractoriness in multiple tumor cohorts•Pathway-based clustering reveals 5 subtypes validated in independent cohorts Patients with high-grade serous ovarian cancers (HGSOCs) have a poor outcome, with the standard of care not having changed over the decades. A detailed characterization of the proteogenomic landscape of HGSOCs across multiple cohorts and validation studies identifies a distinct signature that predicts with high specificity a subset of patients with chemotherapy-refractory cancers and implicates potential therapeutic vulnerabilities.