System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish

PubMed: 42588655 DOI: 10.3390/cancers18152437

Oxidative DNA Damage Is Associated with Immune Remodeling and Therapeutic Response in High-Grade Serous Ovarian Cancer.

Cancers (Basel) 18(15)

Authors: Carson C Edwards, Jenna M Hedlich-Dwyer, Jianqing Zhang, Valeria L Dal Zotto, Dongquan Chen, Rebecca C Arend, Natalie R Gassman

Affiliations

  • Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Department of Medicine, Division of General Internal Medicine & Population Science, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Abstract

Background/Objectives: High-grade serous ovarian cancer (HGSOC) shows variable response to platinum-based neoadjuvant chemotherapy (NACT), with outcomes strongly linked to upfront treatment sensitivity. We evaluated whether oxidative DNA damage in pathologic samples is associated with improved clinical outcomes and reflects tumor-immune interactions. Methods: We analyzed matched pre- and post-NACT tumors from patients with stage III-IV HGSOC using Repair Assisted Damage Detection (RADD) to quantify total and oxidative DNA lesions (oxRADD). Gene expression profiling was performed on a subset of tumors using the NanoString PanCancer I/O 360. Associations with homologous recombination status, platinum sensitivity, recurrence, and survival were assessed. Results: Higher pre-NACT oxidative DNA damage was observed in tumors from patients who later recurred. Among recurrent tumors, elevated oxidative lesions were associated with improved overall survival (61.8 vs. 35.0 months; HR = 0.42, p = 0.037). Oxidative damage predicted recurrence (AUC = 0.71), supporting its utility in risk stratification. Tumors with serious oxidative damage showed reduced IDO1 and TGFβ signaling signatures, along with decreased B cell- and T cell-associated TIGIT signatures after NACT. Conclusions: These findings identify oxidative DNA damage as a potential pretreatment biomarker associated with recurrence, survival, and tumor-immune state, supporting its potential to impact therapeutic decision-making in HGSOC.

MeSH

Cells, Ovary, Neoplasms, Adaptive Immunity, Oxidative Stress, Ovarian Neoplasms, Therapeutics, Wounds And Injuries, Dna Damage