Abstract 981: Validation of the ovarian tumor tissue analysis consortium stratified prognosis of ovarian tumors score using RNAseq and among Black women
Authors: Lindsay Jane Collin, Courtney E. Johnson, Natalie Davidson, Casey S. Greene, Joellen M. Schildkraut, Jennifer A. Doherty
Journal: Cancer Research (2025)

Abstract Background: Ovarian cancer is highly fatal, and Black women are 30% more likely to die of ovarian cancer than white women. The Ovarian Tumor Tissue Analysis consortium Stratified Prognosis of Ovarian Tumors (OTTA-SPOT) gene expression signature demonstrates prognostic potential for high-grade serous ovarian cancers (HGSC) but was developed and validated in a predominately white population, using a NanoString assay. Translating the NanoString assay to RNA sequencing (RNAseq) data and replication across racial and ethnic groups will facilitate broader applications of the signature and is essential for health equity. Therefore, we evaluated the performance of the OTTA-SPOT score when translating from NanoString to RNAseq and across Black and white HGSC patients. Methods: We included 272 self-identified Black and 316 self-identified white HGSC patients from the African American Cancer Epidemiology Study and the North Carolina Ovarian Cancer Study. RNA was extracted from formalin-fixed paraffin-embedded tumor tissues. Gene expression was assessed via RNAseq. We 85th percentile per-gene quantile normalized the RNAseq data to match the equivalent NanoString array of the 101 genes in the OTTA-SPOT score. Each HGSC case was assigned an OTTA-SPOT score using a weighted linear combination of age at diagnosis, stage, and the 101 genes. Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) associating quintiles (third quintile referent category) of the OTTA-SPOT score with all-cause mortality. Results: The RNAseq-derived OTTA-SPOT score performed well among white HGSC cases, but the magnitudes of the HRs were attenuated in Black cases. In white cases, HRs and 95%CIs for the first and fifth quintiles were: HR=0.62 (95%CI: 0.42, 0.92) and HR=2.21 (95%CI: 1.48, 3.30), respectively; among Black cases, corresponding HRs and 95%CIs were: HR=0.98, (95%CI: 0.61, 1.56) and HR=1.13 (95CI: 0.72, 1.77), respectively. The proportion of Black HGSC was lower (42%) in the first quintile compared with the fifth quintile (53%), relative to white HGSC patients (58% and 47%, respectively). Median survival time varied from 7.5 years (IQR: 3.5, 14.5) in the lowest quintile compared with 2.8 years (IQR: 2.0, 4.3) in the highest quintile for white HGSC cases and 6.0 years (IQR: 3.4, 11.5) and 3.4 years (IQR: 2.0, 5.2) for Black HGSC cases. Conclusions: We observed that the RNAseq-derived OTTA-SPOT score yielded reproducible results in Black and white HGSC cases. However, results were more comparable with the original OTTA-SPOT findings among white HGSC cases than Black HGSC cases. More Black HGSC cases were also classified in the highest quintiles of the score. These results highlight the need for the representation of diverse populations in ovarian cancer research to ensure that prognostic signatures will be beneficial to all patients. Citation Format: Lindsay Jane Collin, Courtney E. Johnson, Natalie Davidson, Casey S. Greene, Joellen M. Schildkraut, Jennifer A. Doherty. Validation of the ovarian tumor tissue analysis consortium stratified prognosis of ovarian tumors score using RNAseq and among Black women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 981.