BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Inflammation
Integrating Chronic Inflammation and Hypoxia: The Potential Role of HIF-1α in Tumor Behavior and Therapy Response in High Grade Ovarian Carcinoma
Katarina Černe 1
Sara Polajžer 1
Borut Kobal 2
David Lukanović 2
Erik Škof 3
1. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
2. Univerity Medical Centre Ljubljana, Ljubljana, Slovenia
3. Onkoloski Institut Ljubljana, Ljubljana, Slovenia
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Abstract
High-grade serous ovarian carcinoma (HGSOC) is marked by late diagnosis and chemoresistance, partly driven by chronic inflammation and hypoxia in the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) is a key regulator of these processes; however, its spatial distribution, interaction with inflammation, and effect on chemotherapy response in HGSOC remain unclear. This retrospective study included 28 advanced HGSOC patients treated with neoadjuvant chemotherapy (NACT). Samples were collected at primary surgery (PS) (ovarian and peritoneal tissue, plasma, ascites) and post-NACT at interval debulking surgery (IDS) (omentum, peritoneal tissue, plasma). HIF-1α mRNA expression varied by site, with higher levels in omental and peritoneal tissues compared to ovarian tissue. Plasma and ascites concentrations were significantly correlated, although the mean ascites concentration was lower. Elevated HIF-1α concentration in ascites and plasma at baseline correlated with ESR (erythrocyte sedimentation rate) >30 mm/h, which was also correlated with BRCA mutation status. No correlation was found between HIF-1α and CRP (C-reactive protein) levels. Higher HIF-1α concentrations in ascites and plasma were linked to poor chemotherapy response (CRS1) at IDS. No significant changes in plasma HIF-1α, ESR, or peritoneal HIF-1α mRNA expression were observed before and after chemotherapy. Increased peritoneal HIF-1α at baseline showed a trend toward shorter progression-free survival. These findings suggest that HIF-1α may reflect hypoxia-inflammation crosstalk associated with chemoresistance and progression in HGSOC. The hypoxic-inflammatory microenvironment appears to persist despite chemotherapy and could contribute to ongoing disease activity. However, these observations require validation in independent cohorts before any prognostic or predictive implications can be considered.
Summary
Keywords
Body Fluids, chronic inflammation, HIF-1α, high-grade serous ovarian carcinoma, Neoadjuvantchemotherapy, tumor tissue
Received
30 November 2025
Accepted
20 February 2026
Copyright
© 2026 Černe, Polajžer, Kobal, Lukanović and Škof. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Katarina Černe
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