Cell-Type-Resolved Proteomics Reveals Distinct Immune and Metabolic Programs Between Primary and Recurrent Ascites in HGSOC.

Authors

Bo Ren, Kenneth Weke, Darryl Hardie, Sarah MacPherson, Javier A Alfaro, Julian J Lum, David R Goodlett

Published in

Proteomics. Clinical applications. Volume 20. Issue 5. Pages e70053.

Abstract

High-grade serous ovarian carcinoma (HGSOC) frequently recurs after platinum-taxane therapy, yet recurrence-associated changes within ascites remain unclear. We performed cell-type-resolved quantitative proteomics on paired ascites samples collected at primary diagnosis and at disease recurrence from three HGSOC patients, profiling unsorted cells alongside matched CD45^- tumor-enriched and CD45⁺ immune-enriched fractions. Conventional proteomic label-free quantitative (LFQ) analysis yielded limited significant proteins due to inter-patient heterogeneity. To address this, we applied Gene Set Enrichment Analysis (GSEA) to identify coordinated pathway-level alterations associated with recurrence. Across all cellular compartments, recurrent samples exhibited consistent downregulation of interferon-α/γ-associated pathways alongside enrichment of oxidative phosphorylation and stress-adaptive metabolic programs. In the CD45⁺ immune compartment, these changes were accompanied by enhanced IL-2/STAT5 signaling and reduced antigen-presentation pathways. Together, these findings suggest that recurrent ascites is characterized by a shift toward oxidative metabolism and a more immunosuppressive microenvironment.

PMID:
42610661
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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