For a study, researchers sought to understand that numerous outcomes and treatment responses have been linked to the characteristics of the genome and transcriptome. The connections between changes in gene copy number, gene expression, and gene sequencing were still unclear. To assess the link between patient subgroups denoted by certain molecular events, they performed multiomic characterization on a large High-grade serous ovarian carcinoma (HGSOC) cohort (n=362) with extensive clinical annotation. With multivariable hazard ratios (HR) of 0.40 and 0.51, respectively, the first- and second-line treatment response rates were significantly greater in the BRCA2-mutant (BRCA2m) and EMSY-overexpressing cases. Shorter survival times and underrepresentation of FIGO stage IV cases were observed in CCNE1-gained (CCNE1g) cases, but there was no obvious change in treatment responsiveness. Investigators showed that the subtypes derived from the TCGA and Tothill substantially overlap. PRO/C5 cases exhibited the highest CCNE1g frequency (23.9%, 22.2%) and consistently low immune cell infiltration, whereas IMR/C2 cases had a higher BRCA1/2m frequency (25.5%, 32.5%) and significantly more immune cell infiltration. All transcriptome subtypes showed the survival benefit for people with faulty homologous recombination repair (HRR) genes (HR range, 0.48–0.68). Significant RB loss was related to increased survival in cases of HRR gene aberrations, while significant HRR gene aberrations co-occurred with RB loss (multivariable HR, 0.50). These data provided a high-resolution image of the molecular environment in HGSOC, which facilitated the identification of patients who might benefit from specific molecular therapies and identifying patients who required novel treatment modalities for improved outcomes.

Source:

aacrjournals.org/clincancerres/article/28/16/3546/707393/Multiomic-Characterization-of-High-Grade-Serous