The role of hepatocyte growth factor activator inhibitor-1 (HAI-1) as a prognostic indicator in cervical cancer.
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.
Nakamura
Keiichiro
K
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan. k-nakamu@cc.okayama-u.ac.jp
Abarzua
Fernando
F
Hongo
Atsushi
A
Kodama
Junichi
J
Nasu
Yasutomo
Y
Kumon
Hiromi
H
Hiramatsu
Yuji
Y
D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D053491:Proteinase Inhibitory Proteins, Secretory / Q000032:analysis / Q000502:physiology*; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology
D014408:Biomarkers, Tumor; D053491:Proteinase Inhibitory Proteins, Secretory; C109149:SPINT1 protein, human