Overcoming intra-tumoral heterogeneity for biomarker discovery in the high-grade serous ovarian cancer proteome
Improved biomarkers of treatment response are needed for patients with high-grade serous ovarian cancer (HGSC). A challenge is substantial anatomical site-to-site variation in expression. We completed data-independent acquisition-mass spectrometry (DIA-MS) analysis of 404 fresh frozen and 78 formalin-fixed, paraffin-embedded HGSC tissue samples from the ovary (adnexal) and a common secondary site (omentum) in 11 patients. This was compared with mutation testing, gene expression, and whole-genome copy number profiling. Proteins with relatively stable intra- and variable inter-individual expression (n = 1651), included a 52-protein module reflecting interferon-mediated tissue inflammation, indicative of a cGAS-STING pathway cytosolic double-stranded (ds) DNA response. The dsDNA sensing/inflammation score was higher in the omentum compared with the ovary. Ovarian HGSC samples showed marked inter-individual differences in inflammatory and immune responses to DNA damage. Stable discriminative features of the HGSC proteome, a prerequisite for clinical predictive biomarkers, are detectable in ovary (adnexal) tissue samples.
Authors
- Peter G. Hains (ORCID: https://orcid.org/0000-0002-7276-1760)
- Phillip J. Robinson (ORCID: https://orcid.org/0000-0002-7878-0313)
- Swetansu Pattnaik (ORCID: https://orcid.org/0000-0003-3598-7733)
- Natasha Lucas (ORCID: https://orcid.org/0000-0002-7656-6866)
- Roger R. Reddel (ORCID: https://orcid.org/0000-0002-6302-6107)
- Anna DeFazio (ORCID: https://orcid.org/0000-0003-0057-4744)
- David D.L. Bowtell (ORCID: https://orcid.org/0000-0001-9089-7525)
- Sivatharsny Srirangan (ORCID: https://orcid.org/0000-0002-9737-066X)
- Daniel Bucio-Noble (ORCID: https://orcid.org/0000-0001-7603-8732)
- Maiken Marcker Espersen
- Srikanth S. Manda (ORCID: https://orcid.org/0000-0003-1690-8403)
- Qing Zhong
- Dylan Xavier (ORCID: https://orcid.org/0000-0003-2601-9343)
- Sadia Mahboob (ORCID: https://orcid.org/0000-0002-1143-8935)
- Catherine J. Kennedy (ORCID: https://orcid.org/0000-0002-4465-5784)
- Cristina Mapagu (ORCID: https://orcid.org/0000-0003-0403-7444)
- Jessica Boros (ORCID: https://orcid.org/0000-0002-4090-4253)
- Natalie Bouantoun
- Ahwan Pandey (ORCID: https://orcid.org/0000-0003-2238-1054)
- Alison H. Brand (ORCID: https://orcid.org/0000-0001-7975-6326)
- Dale W. Garsed (ORCID: https://orcid.org/0000-0003-1223-0121)
- Brett Tully (ORCID: https://orcid.org/0000-0001-6892-2771)
- Rosemary L. Balleine (ORCID: https://orcid.org/0000-0003-2864-4345)
- Yoke-Eng Chiew
Institutions
- The University of Sydney (AU)
- Garvan Institute of Medical Research (AU)
- Children's Medical Research Institute (AU)
- Peter MacCallum Cancer Centre (AU)
- Nepean Hospital (AU)
- Westmead Hospital (AU)
- Westmead Institute for Medical Research (AU)
- Cancer Council NSW (AU)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-06-11
- DOI
- https://doi.org/10.1038/s41698-025-00911-y
- Citations
- 1
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 1.52
Funders
- Children's Medical Research
- Victorian Cancer Agency
- Marshfield Clinic Research Foundation
- Ovarian Cancer Australia
- David and Elaine Potter Foundation
- European Commission
- Australian Cancer Research Foundation
- National Breast Cancer Foundation
- Ian Potter Foundation
- Cancer Australia
- Cancer Institute NSW
- University of Sydney
- Peter MacCallum Cancer Centre
- NSW Ministry of Health
- Horizon 2020 Framework Programme
- Medical Research Council
- National Health and Medical Research Council
- Cancer Council South Australia
- Cancer Council Victoria
- Cancer Council NSW
- Cancer Council Tasmania
- Cancer Council Western Australia
- National Cancer Institute
- Medical Research and Materiel Command