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Int J Oncol. 2009 Aug;35(2):239-48.

The role of hepatocyte growth factor activator inhibitor-1 (HAI-1) as a prognostic indicator in cervical cancer.

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Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.


Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a Kunitz-type serine protease inhibitor that has a broad inhibitory spectrum against serine proteases. This is the first study to investigate the role of HAI-1 and its clinical importance in cervical cancer. We attempted to investigate the inhibitory effects of HAI-1 using cervical carcinoma cell lines SiHa with integrated human papillomavirus (HPV) 16 and HeLa with integrated HPV 18. HAI-1 expression in cervical cancer (n=91) were assessed by immunohistochemistry. HAI-1 was found to be a potential inhibitory effects mediated by reduction of hepsin, matriptase and prostasin expression. This led to apoptosis through a reduction in the levels of Bcl-2, Bcl-xL, MUPP-1 and MAGI-3 in cervical cancer cell lines. There were significant correlations between HAI-1 expression and stage (p=0.013), tumor size (p=0.002), stromal invasion (p<0.001), vaginal invasion (p=0.031), parametrial invasion (p=0.012), lymph-node metastasis (p=0.019), and LVS involvement (p=0.002). The disease-free and overall survival rates of patients exhibiting high HAI-1 expression were significantly higher than those of patients exhibiting low HAI-1 expression (p=0.022 and p=0.011, respectively). The present study proposes that these findings may be considered HAI-1 as a therapeutic target for treatment and identify as a favorable prognostic marker for cancer patients of cervical cancer.

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