Overcoming intra-tumoral heterogeneity for biomarker discovery in the high-grade serous ovarian cancer proteome

Manda, SS; Espersen, MM; Mapagu, C; Bouantoun, N; Boros, J; Chiew, YE; Srirangan, S; Pattnaik, S; Kennedy, CJ; Brand, AH; Garsed, DW; Pandey, A; Bowtell, DDL; Australian Ovarian Cancer Study (AOCS) Group; Lucas, N; Xavier, D; Mahboob, S; Bucio-Noble, D; Tully, B; Hains, PG; Robinson, PJ; Zhong, Q; Reddel, R; DeFazio, A; Balleine, RL

Author(s): Manda, SS; Espersen, MM; Mapagu, C; Bouantoun, N; Boros, J; Chiew, YE; Srirangan, S; Pattnaik, S; Kennedy, CJ; Brand, AH; Garsed, DW; Pandey, A; Bowtell, DDL; Australian Ovarian Cancer Study (AOCS) Group; Lucas, N; Xavier, D; Mahboob, S; Bucio-Noble, D; Tully, B; Hains, PG; Robinson, PJ; Zhong, Q; Reddel, R; DeFazio, A; Balleine, RL;
Details: Publication Year 2025-06-11,Volume 9,Issue #1,Page 172
Journal Title: NPJ Precision Oncology
Publication Type: Research article
Abstract: 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.
Publisher: Springer Nature
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1038/s41698-025-00911-y
Open Access at Publisher's Site: https://doi.org/10.1038/s41698-025-00911-y
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-07-31 04:18:37

Last Modified: 2025-07-31 04:18:59