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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414761/
https://www.ncbi.nlm.nih.gov/pubmed/37541199
http://dx.doi.org/10.1016/j.cell.2023.07.004
Descripción
Sumario: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.

Ejemplares similares