HIF1α is an independent prognostic factor for overall survival in advanced primary epithelial ovarian cancer - a study of the OVCAD Consortium

HIF1α 是晚期原发性上皮性卵巢癌总体生存率的独立预后因素 - OVCAD 联盟的一项研究

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作者:Elena Ioana Braicu, Hrvoje Luketina, Rolf Richter, Dan Cacsire Castillo-Tong, Sandrina Lambrechts, Sven Mahner, Nicole Concin, Monika Mentze, Robert Zeillinger, Ignace Vergote, Jalid Sehouli

Conclusion

HIF1α overexpression in ovarian cancer is associated with poor overall survival, underlining the importance of hypoxia in this angiogenesis driven disease.

Methods

In this multicentric study, 275 patients with advanced primary epithelial ovarian cancer were included. All patients underwent cytoreductive surgery with maximal surgical effort and adjuvant platinum-based chemotherapy. HIF1α expression was analyzed in tissue lysates, using an enzyme-linked immunosorbent assay.

Purpose

Hypoxia is a common phenomenon encountered in solid cancers, leading to chemotherapy resistance and therefore to aggressiveness of the disease. The homeostatic response to hypoxia is mediated by hypoxiainducible factor-1 (HIF-1). The aim of this study was to investigate the impact of HIF1α in patients with primary epithelial ovarian cancer.

Results

HIF1α was detected in 79.3% of the tissue samples. Patients with increased HIF1α expression (cutoff: 80 pg/mg protein) in tumoral tissue lysates were more likely to have less favorable survival. HIF1α (P=0.009, hazard ratio [HR] 2.505, 95% confidence interval [95% CI] 1.252-5.013) together with International Federation of Gynecology and Obstetrics (III versus IV) (P=0.013, HR 0.540, 95% CI 0.332-0.878), histology (P=0.007, HR 2.748, 95% CI 1.315-5.743), presence of peritoneal carcinomatosis (P=0.014, HR 2.176, 95% CI 1.170-4.046), residual tumor mass (P=0.017, HR 1.641, 95% CI 1.091-2.468), and response to platinum-based chemotherapy (P<0.001, HR 8.131, 95% CI 5.13-12.88) were independent prognosis factors for overall survival. The independent prognostic factors for progression-free survival were International Federation of Gynecology and Obstetrics stage (P=0.01), histological subtypes (P=0.016), and presence of peritoneal carcinomatosis (P<0.05).

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