Fig. 1: Proteogenomic analysis of high-grade serous ovarian cancer (HGSOC).

a Bulk tumor (BT) and laser microdissection (LMD) enriched tumor (ET) epithelium from adnexal (n = 48) and metastatic (n = 22) HGSOC tumor specimens were prepared and DNA, RNA, and protein extracts were profiled by deep whole genome sequencing, RNA sequencing, and proteomics by mass spectrometry and reverse phase protein arrays; LMD was also used to collect stromal cell populations for a subset of cases (n = 48) for proteomics (Created in part with BioRender.com). b Hierarchical cluster analysis of somatic mutations (tumor protein 53, TP53), breast cancer type 1 and 2 susceptibility protein (BRCA1/2), cyclin-dependent kinase 12 (CDK12), copy number variation (cyclin E, CCNE1), SNV, and SV signatures previously investigated in HGSOC, and sum SNV and SV statistics per case in whole genome sequencing (WGS) data from BT collections. c Comparison of gene-wise protein and transcript correlations (5721 protein:transcript pairs) between BT data with HGSOC data from CPTAC HGSOC cohort (Spearman Rho = 0.598, p < 0.0001). d Comparison of protein and transcript correlations by molecular subtypes (ConsensusOV classifications, DIF – differentiated, IMR – immunoreactive, MES – mesenchymal, PRO – proliferative) classified using BT transcriptome data (n = 70) as well as for the CPTAC HGSOC cohort (n = 169); *designates p-values corresponding to Mann–Whitney U (MWU), p < 0.1, ** MWU p < 0.05, *** MWU p < 0.005. e Hierarchical analysis of consensus clusters calculated from the top 25% variably abundant proteins from 70 APOLLO-2 HGSOC BT proteome data. f Kaplan–Meier plot of overall survival in patients with tumors harboring high (MES_Upper: upper quartile, n = 18) versus low (MES_Lower: lower quartile, n = 52) correlation with nine prognostic proteins significantly elevated in MES vs DIF & PRO tumors (Log Rank, p = 0.017). g Kaplan–Meier overall survival curves from a 9-candidate expression signature correlating with differential tumor purity from an independent HGSOC cohort (n = 126)¹⁵ (Log-Rank, p = 0.011).