Cyclin E1 overexpression identifies a therapeutically relevant poor prognostic patient subgroup in high-grade serous ovarian cancer

Cyclin-E1 protein overexpression, including through CCNE1 gene amplification, is recognized as a poor prognostic factor in high-grade serous ovarian cancer (HGSOC) and is a promising predictive marker for investigational therapies targeting cell-cycle checkpoints. However, the demonstration of its clinical utility remains elusive due to inconsistent definitions of protein overexpression and gene amplification. This study characterizes Cyclin-E1 overexpression and CCNE1 amplification prevalence and prognostic value in HGSOC using both original and public clinical cohorts. Fifty-nine percent of tumors overexpressed Cyclin-E1, more than half of which had no evidence of CCNE1 gene amplification. The prevalence of CCNE1 amplification varied across studies and was higher in interventional studies. Patients with Cyclin-E1 positive tumors had poorer outcomes after adjuvant therapy. Platinum-based chemotherapy increased Cyclin-E1 expression. These patients were less likely to benefit from PARP inhibitors (75% are BRCA-wildtype) or mirvetuximab-soravtansine (67% were not FRα-high), highlighting a distinct patient population in need of novel therapies.

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Journal
npj Precision Oncology
Published
2026-05-30
DOI
https://doi.org/10.1038/s41698-026-01519-6
Primary Topic
Cancer-related Molecular Pathways
Type
article
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article

Cyclin E1 overexpression identifies a therapeutically relevant poor prognostic patient subgroup in high-grade serous ovarian cancer

Jinkil Jeong, Céline Gavoille, Heekyung Chung, Christophe Desauw et al.
npj Precision Oncology
Cancer-related Molecular Pathways
article

Cyclin E1 overexpression identifies a therapeutically relevant poor prognostic patient subgroup in high-grade serous ovarian cancer

Jinkil Jeong, Céline Gavoille, Heekyung Chung, Christophe Desauw, Olivier Harismendy, D. Rajendran, Nandini Molden, Doris Kim, Elisa Yaniz‐Galende, Danielle D. Jandial, Chan-Sup Shim, Alexandra Levy, Fiona Simpkins, James Yen, Funda Meric‑Bernstam, Jianhui Ma, Alexandra Leary, Mark R. Lackner, Nathalie Bonichon-Lamichhane, Joyce F. Liu, Leslie M. Randall, Felix Blanc-Durand, Véronique D’Hondt, Philippe Follana, Mona Abed, Stéphane Oudard
article en

Abstract

Cyclin-E1 protein overexpression, including through CCNE1 gene amplification, is recognized as a poor prognostic factor in high-grade serous ovarian cancer (HGSOC) and is a promising predictive marker for investigational therapies targeting cell-cycle checkpoints. However, the demonstration of its clinical utility remains elusive due to inconsistent definitions of protein overexpression and gene amplification. This study characterizes Cyclin-E1 overexpression and CCNE1 amplification prevalence and prognostic value in HGSOC using both original and public clinical cohorts. Fifty-nine percent of tumors overexpressed Cyclin-E1, more than half of which had no evidence of CCNE1 gene amplification. The prevalence of CCNE1 amplification varied across studies and was higher in interventional studies. Patients with Cyclin-E1 positive tumors had poorer outcomes after adjuvant therapy. Platinum-based chemotherapy increased Cyclin-E1 expression. These patients were less likely to benefit from PARP inhibitors (75% are BRCA-wildtype) or mirvetuximab-soravtansine (67% were not FRα-high), highlighting a distinct patient population in need of novel therapies.

npj Precision Oncology
Inova Health System (US), The University of Texas MD Anderson Cancer Center (US), Zen-Noh (Japan) (JP), Institut Gustave Roussy (FR), Centre Hospitalier Universitaire de Lille (FR), Hôpital Européen Georges-Pompidou (FR), Délégation Centre-Est (FR), Dana-Farber Cancer Institute (US), Arcagy Gineco (FR), Tracon Pharmaceuticals (United States) (US), Institut de Recherche en Cancérologie de Montpellier (FR), Eau de Paris (France) (FR), Centre Antoine Lacassagne (FR), University of Pennsylvania (US)
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Openalex Percentile: Top 6%
Cancer-related Molecular Pathways
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