20.500.12556/DiRROS-28615 Integrating chronic inflammation and hypoxia the potential role of HIF-1α in tumor behavior and therapy response in high-grade serous ovarian cancer 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-1a) 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-1a 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-1a 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-1a and CRP (C-reactive protein) levels. Higher HIF-1a concentrations in ascites and plasma were linked to poor chemotherapy response (CRS1) at IDS. No significant changes in plasma HIF-1a, ESR, or peritoneal HIF-1a mRNA expression were observed before and after chemotherapy. Increased peritoneal HIF-1a at baseline showed a trend toward shorter progression-free survival. These findings suggest that HIF-1a 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. body fluids chronic inflammation HIF-1a high-grade serous ovarian carcinoma neoadjuvant chemotherapy tumor tissue telesne tekočine kronično vnetje visokostopenjski serozni karcinom jajčnikov neoadjuvantna kemoterapija tumorsko tkivo true false true Angleški jezik Slovenski jezik Neznano 2026-03-26 08:46:25 2026-03-26 08:46:26 2026-03-27 04:14:46 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Opis vira z dne 11. 3. 2026; str. 1-10 iss [article no.] 1757708 Vol. 17 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-097 1664-3224 10.3389/fimmu.2026.1757708 271315203 RAZ_Polajzer_Sara_2026.pdf RAZ_Polajzer_Sara_2026.pdf 1 1FDDDAE28717C862AE665B3E3823AF90 a877c2e018187ff665ee95ffd914efdeb74867ee0909a5d0432a7c910d55e727 086d4ce8-28e8-11f1-aa40-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=42509 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1757708/full 1 e55dcc42-28e7-11f1-aa40-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=42508 Univerzitetni klinični center Ljubljana 0 0 0