Hepatocyte growth factor activator inhibitor-2 (HAI-2) is a favorable prognosis marker and inhibits cell growth through the apoptotic pathway in cervical cancer.
BACKGROUND
In light of the poor prognosis for cervical cancer, research continues into the development of innovative and efficacious treatment modalities for this disease. We investigated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) and evaluated its clinical importance in cervical cancer.


METHODS
HAI-2 expression was examined in cervical cancer specimens (n=52) by immunohistochemistry. We further attempted to investigate the biological functions and inhibitory effects of HAI-2 using human papillomavirus (HPV) 16 type SiHa and HPV 18 type HeLa cervical cancer cell lines.


RESULTS
There were significant correlations between HAI-2 expression and stage (P=0.017), lymph node metastasis (P=0.005) and ovarian metastasis (P=0.038). Low HAI-2 expression was a significant predictor for a poor prognosis compared with high HAI-2 expression (disease-free survival rate, P=0.016; overall survival rate, P=0.021). After transient transfection into the SiHa and HeLa cell lines, HAI-2 showed potential inhibitory effects mediated by reductions in hepsin and matriptase expression, which led to apoptosis by increasing the level of Bak and reducing the level of Bcl-2.


CONCLUSIONS
The present findings indicate that low HAI-2 expression in cervical cancer may be associated with a poor prognosis. We propose that HAI-2 may represent a therapeutic target for the treatment of cervical cancer.
Nakamura
K
K
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical Sciences, Okayama, Japan. k-nakamu@cc.okayama-u.ac.jp
Abarzua
F
F
Hongo
A
A
Kodama
J
J
Nasu
Y
Y
Kumon
H
H
Hiramatsu
Y
Y
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018196:Carcinoma, Adenosquamous / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human