Proteogenomic Analysis of Enriched Tumor Epithelium Identifies Prognostic Signatures and an Increased Dependency of Homologous Recombination Proficient Cells on BMI1 in High Grade Serous Ovarian Cancer

ABSTRACT: Although several proteogenomic analyses of high-grade serous ovarian cancer (HGSOC) have been conducted, these analyses are often dominated by tissues with high levels of tumor cell nuclei (purity), despite low purity being associated with worse outcome. We performed deep proteogenomic profiling of bulk tumor (BT) and laser microdissection (LMD) enriched tumor (ET) and stromal (ST) cell populations from 70 HGSOC patient tumors spanning a broad spectrum of purity. We identified a cluster of patients with longer progression free survival associated with increased immune signatures and validated proteins correlating with tumor infiltrating lymphocytes (TILs) in 65 tumors collected from an independent cohort of 12 HGSOC patients, as well as with overall survival in an additional cohort of 126 HGSOC patients. We identified that homologous recombination deficient (HRD) tumors express transcriptomic and proteomic pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts, including 69 HRD-positive HGSOC tumors. In summary, our proteogenomic analysis provides important new clinically relevant insights into HGSOC tumor cell populations, and have uncovered prognostic proteogenomic alterations correlating with TILs, low tumor purity, as well as expression alterations associated with HRD status and immune infiltration.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Ovarian Serous Carcinoma Cell, Stromal Cell, Epithelial Ovarian Cancer Cell

DISEASE(S): Ovarian Serous Carcinoma,Malignant Neoplasm Of Ovary

SUBMITTER: Thomas Conrads  

LAB HEAD: Thomas P.

PROVIDER: PXD045417 | Pride | 2024-03-15

REPOSITORIES: Pride