Dataset Information

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

ACCESS DATA

Publications

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

Similar Datasets

Project description:Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for non-transplant indications, could regulate specific CRM genes and reduce the number of graft infiltrating cells during acute rejection. We treated mice with HLA-mismatched murine cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatina on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning and rational drug design. The eight transplant data sets used for discovery include GSE4315, GSE2596, GSE4470, GSE9377, GSE1563, GSE9493, GSE13440, GSE6095. The two additional independent cohorts of 151 transplant biopsies are GSE25902 and GSE1563. Not all samples from all studies were used. Only the samples marked as either AR or STA in each data set were used for analysis. The 101 samples in this study were used as case-control experiment between acute rejection (AR) and stable (STA) in renal transplant. The samples in this series are one of the three independent validation cohorts. The other two cohorts are described in GSE21374 and GSE36059

Dataset Information

Proteogenomic analysis of chemo-refractory high grade serous ovarian cancer

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets