OP022/#597 Optimizing the number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma: a propensity-score matching analysis

Abstract

Objectives To identify gene expression profiles and interacting pathways in BRCA1- and BRCA2- associated high grade serous ovarian cancer (HGSOC) as compared to one another and to BRCA wild type, homologous recombination proficient (HRP) tumors. Methods of total samples, and HRP were analyzed. Gene was collected from Tempus and were to identify differ-entially expressed genes (DEG) with p-value and fold change of Meta and pathway analyses were performed among BRCA1, BRCA2 and HRP groups using Venn diagram and Advaita Bio ’ s iPathwayGuide. BRCA mutated and wild type (wt) ID8 mouse cell lines were used for protein expression and seahorse assay for metabolism analysis. Results From 18,284 genes with measured expression, 843 (4.6%) DEG were found between BRCA2 vs BRCA1, 748 (4.1%) between BRCA2 vs HRP and 1,858 (10.2%) between BRCA1 and HRP. On meta-analysis of the three comparisons, pathway analysis revealed significant involvement of Wnt signaling pathway and oxidative phosphorylation unique to BRCA2 group compared to fibroblast growth factor signaling PI3K-Akt signaling for BRCA1. Western blot analysis con-firmed higher expression of oxidative phosphorylation com-plex proteins in BRCA1/BRCA2 mutated lines and differential expression of b catenin between BRCA mutated versus wt cell lines. Seahorse assay showed higher oxidative consumption rate in BRCA mutated versus wt cells. Conclusions Our study identified differential pathway regula-tion for BRCA2 versus BRCA1 associated HGSOC, suggesting each should be considered a separate phenotype with unique opportunities for targeted therapy.