Hypoxia-induced Maspin Expression Affects the Prognosis of Ovarian Clear Cell Carcinoma

Eun Ji Lee, Soo Jin Park, Cheol Lee, Ga Won Yim, Jae Weon Kim, Hee Seung Kim

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background/Aim: To investigate the role of the expression of hypoxia-related genes on the prognosis of ovarian clear cell carcinoma (OCCC). Materials and Methods: Basal mRNA levels of eight hypoxia-related genes were compared. Cell viability was assayed after treating ES-2 cells under hypoxic conditions. The mRNA and protein levels were evaluated after the induction of hypoxia and administration of increased doses of N-acetylcysteine (NAC). Finally, the prognostic role of their expression levels was evaluated in 61 patients with OCCC. Results: The mRNA and protein levels of maspin increased gradually with the induction of hypoxia. Maspin protein expression decreased after treatment with paclitaxel and NAC. High expression of maspin was related to poor progression-free and overall survival in patients with OCCC (adjusted hazard ratios, 3.97 and 7.47; 95% confidence intervals=1.34-11.81, and 1.98-28.13). Conclusion: High expression of maspin induced by hypoxia might be associated with poor prognosis of OCCC. Ovarian cancer is a heterogeneous group of diseases and consists of different histologic types, demonstrating distinct biological properties (1). Even though type II ovarian cancers, including high grade serous carcinoma, have valuable biomarkers such as CA-125 and human epididymis protein 4, there are few diagnostic or prognostic biomarkers for type I ovarian cancers representing low-grade serous, mucinous, endometrioid, and clear cell carcinoma (2). Thus, it is difficult to predict the clinical prognosis of type I ovarian cancers due to the lack of biomarkers (3). Since previous studies demonstrated the correlation between hypoxia and ovarian cancer progression (4, 5), further investigations for identifying new biomarkers related to hypoxia are still meaningful. Among them, ovarian clear cell carcinoma (OCCC) shows rather unique entity in terms of clinical, genetic, and histological features (6). Notably, chronic inflammation and oxidative stress in precancerous lesions such as endometriosis have been suggested to trigger its malignant transformation to OCCC (7, 8). Although hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) are related to carcinogenesis and progression of ovarian cancer by inducing chemo-resistance (9-11), other hypoxia-related genes such as HIF-1β, cAMP-response element-binding protein-binding protein (CBP), adenovirus early region 1A-binding protein P300 (P300), factor-inhibiting hypoxia-inducible factor (FIH), von Hippel-Lindau (VHL), and maspin have not been investigated sufficiently for their roles affecting drug resistance and prognosis. There is also a lack of relevant studies about the role of hypoxia-related genes as prognostic factors in ovarian cancer. Thus, this study aimed to investigate the role of the expression of hypoxia-related genes as potential prognostic biomarkers in type I ovarian cancer, especially OCCC.

Original languageEnglish
Pages (from-to)212-220
Number of pages9
JournalIn Vivo
Volume36
Issue number1
DOIs
StatePublished - Feb 2022

Keywords

  • Clear cell
  • Hypoxia
  • Maspin
  • Ovarian cancer
  • Prognosis

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