Oxford Classic-Defined EMT Risk Stratification of High-Grade Serous Ovarian Cancer for Guiding Treatment Decisions

Rai, L; Ravaggi, A; Bignotti, E; Hollis, RL; Garsed, DW; Pandey, A; Papalois, KB; Patel, F; Kamel, Y; Campo, L; Easton, A; Nulsen, J; Roskams-Hieter, B; Artibani, M; Wang, L; Hussain, N; Wang, L; Zaarour, N; Aggarwal, A; Ahmed-Ebbiary, A; Al-Deka, A; Churchman, M; Herrington, CS; Ardighieri, L; Ferrari, F; Yau, C; Gourley, C; Odicino, F; Ahmed, AA

Author(s): Rai, L; Ravaggi, A; Bignotti, E; Hollis, RL; Garsed, DW; Pandey, A; Papalois, KB; Patel, F; Kamel, Y; Campo, L; Easton, A; Nulsen, J; Roskams-Hieter, B; Artibani, M; Wang, L; Hussain, N; Wang, L; Zaarour, N; Aggarwal, A; Ahmed-Ebbiary, A; Al-Deka, A; Churchman, M; Herrington, CS; Ardighieri, L; Ferrari, F; Yau, C; Gourley, C; Odicino, F; Ahmed, AA;
Details: Publication Year 2026-01-06,Volume 32,Issue #1,Page 188-202
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: PURPOSE: The association between epithelial-to-mesenchymal transition (EMT) in high-grade serous ovarian cancer (HGSOC) and poor prognosis is known. However, molecularly defining a subset of tumors that reproducibly associates with poor prognosis has been an elusive goal in this disease. A molecular signature that can robustly identify patients with poor prognosis and guide treatment decisions, including surgical strategy and targeted therapies, can improve survival rates. EXPERIMENTAL DESIGN: We carried out RNA sequencing of 139 tumor samples (Brescia cohort); an external validation on 362 and 126 patients from the Scottish and Garsed cohorts, respectively; and a meta-analysis of 1,023 tumors to develop clinically useful risk groups. Identification of therapeutic targets was carried out by transcriptomic analyses of fluorescence-activated cell sorted (FACS) tumor epithelial cells and multiplex immunofluorescence assessment of tissue sections. RESULTS: In this study, we have validated the prognostic strength of the Oxford Classic-defined EMT in three independent patient cohorts: Brescia [HR = 3.6; 95% confidence interval (CI) of 1.59-7.97; P = 1.99e-03], Scottish (HR = 1.71; 95% CI of 1.08-2.70; P = 2.23e-02), and Garsed (Kruskal-Wallis P = 0.00071). OxC-based risk stratification of HGSOC could robustly identify poor-risk patients with a 5-year median survival for OxC high-risk and OxC low-risk groups of 13% and 50%, respectively (95% CI of 7.1%-23.5% vs. 36.1%-69.3%) in the Brescia cohort. Further analysis of the risk groups suggests that an alternative surgical strategy and a combination therapy involving EMT targeting drugs and immunomodulators could elicit improved clinical response in poor-risk patients. CONCLUSIONS: This study provides a clinically useful risk stratification strategy for HGSOC, as well as targeted treatment options for high-risk patients. See related commentary by Venegas et al., p. 10.
Keywords: Humans; Female; *Epithelial-Mesenchymal Transition/genetics; *Ovarian Neoplasms/pathology/genetics/therapy/mortality; Prognosis; Neoplasm Grading; *Cystadenocarcinoma, Serous/pathology/genetics/therapy/mortality; *Biomarkers, Tumor/genetics; Middle Aged; Risk Assessment; Aged; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Clinical Decision-Making
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1158/1078-0432.Ccr-24-4250
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-08-26 05:34:24

Last Modified: 2026-01-23 03:46:43