Deciphering brain metastasis in epithelial ovarian cancer: multimodal analysis and potential biomarkers
Epithelial ovarian cancer (EOC) remains the most lethal gynaecological malignancy in developed countries, with recurrence and drug resistance posing significant clinical challenges. Brain metastases (BM) from epithelial ovarian cancer, once rare, are an increasing phenomenon and are characterised by a dismal prognosis. To explore the molecular underpinnings of BM in EOC, we conducted a multimodal genomics and transcriptomics analysis of matched primary tumour and brain metastases samples from a retrospective cohort. Our findings revealed high genomic concordance between primary tumour (PT) and BM, with alterations in key pathways such as MYC (MYC Proto-Oncogene, bHLH Transcription Factor) targets, extracellular matrix remodelling, and inflammatory signalling characterizing the BM. AFP (Alpha-fetoprotein) and GFAP (Glial Fibrillary Acidic Protein) emerged as potential biomarkers from the primary lesion for BM onset, while network analysis identified MET (MET Proto-Oncogene, Receptor Tyrosine Kinase), GDF15 (Growth Differentiation Factor 15), and S100A9 (S100 Calcium Binding Protein A9) as candidate mediators of tumour-brain crosstalk. These results offer new insights into EOC brain tropism, highlighting potential targets for therapeutic intervention and personalized patient management in the precision oncology era.
Authors
- Floriana Camarda (ORCID: https://orcid.org/0000-0002-5206-6867)
- A. Piermattei (ORCID: https://orcid.org/0000-0002-6835-1179)
- Simona Duranti (ORCID: https://orcid.org/0000-0002-1924-238X)
- Davide Cacchiarelli (ORCID: https://orcid.org/0000-0002-9621-6716)
- Marcello Salvi
- Luciano Giacò (ORCID: https://orcid.org/0000-0003-0657-4323)
- Valentina Iacobelli (ORCID: https://orcid.org/0000-0002-5874-3320)
- Luca Mastrantoni (ORCID: https://orcid.org/0000-0003-1853-4927)
- Francesca Sillano
- Masoumeh Karimi (ORCID: https://orcid.org/0000-0003-2455-0894)
- Giuseppina Raspaglio
- Rita Trozzi (ORCID: https://orcid.org/0000-0001-6556-5203)
- Anna Fagotti
- Marianna Buttarelli (ORCID: https://orcid.org/0000-0002-9062-8605)
- Anna Grimaldi (ORCID: https://orcid.org/0000-0002-3957-9780)
- A. Minucci
- Marcella Cesana (ORCID: https://orcid.org/0000-0002-9099-8681)
- Lorenzo Vaccaro (ORCID: https://orcid.org/0000-0002-8233-3241)
- Rosa De Santis (ORCID: https://orcid.org/0000-0001-6473-866X)
- M. Massa
- P. Mattogno
- M. De Donato
- C. Marchetti
- M. C. Sassu
- C. Nero
- G. Scambia
Institutions
- Università Cattolica del Sacro Cuore (IT)
- Agostino Gemelli University Polyclinic (IT)
- Scuola Superiore Meridionale (IT)
- University of the Sacred Heart (JP)
- Telethon Institute Of Genetics And Medicine (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- University of Naples Federico II (IT)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2026-01-19
- DOI
- https://doi.org/10.1038/s41698-025-01206-y
- Primary Topic
- GDF15 and Related Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- AstraZeneca
- GlaxoSmithKline
- Giovanni Armenise-Harvard Foundation
- Intuitive Surgical
- European Commission
- Ministero della Salute
- Associazione Italiana per la Ricerca sul Cancro
- PharmaMar