The role of HE4 in ovarian cancer: inhibiting tumour cell proliferation and metastasis.

Gynecological Oncology Centre, Peking University People's Hospital, Beijing, China.
The Journal of international medical research (Impact Factor: 0.96). 01/2011; 39(5):1645-60.
Source: PubMed

ABSTRACT As a promising biomarker, human epididymis protein 4 (HE4) has been widely used for the early detection and differential diagnosis of ovarian cancer. This study evaluated the function of HE4 in the carcinogenesis and progression of ovarian cancer. An enzyme immunometric assay, used to detect HE4 in the serum of ovarian cancer patients, showed that the protein could discriminate between malignant and benign ovarian tumours with high specificity. An exogenous HE4 gene was transfected into ovarian cancer cell lines and an immortalized ovarian epithelial cell line. Compared with the controls, HE4 overexpression significantly promoted cell apoptosis and adhesion. Overexpression of HE4 also led to significant inhibition of cell proliferation, migration and invasiveness in vitro, as well as xenograft tumour formation in vivo. This is the first report to demonstrate the functional importance of HE4 in multiple cellular processes and indicates that HE4 may play a protective role in the progression of ovarian cancer.

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    ABSTRACT: The aim of our study was to evaluate the behaviour of the human epididymis protein 4 (HE4) in the peritoneal fluid encountered in various female genital diseases. We enrolled 139 patients, 40 with ovarian cancer (group I), 82 with benign diseases (group II), and 17 with other malignant neoplasms (group III). The HE4 tumor marker concentrations were determined in serum, in the peritoneal effusion and ovarian cyst/ tumor fluids, CA125 in the serum only. We compared the groups, examined correlations and determined corresponding ROC curves. We evaluated the relationship between the HE4 marker concentration in the peritoneal effusion in the group I, depending on the selected prognostic parameters. The HE4 median value between the study groups did not differ statistically significantly and were as follows: in group I 3322 pmol/L, in the group II 2150 pmol/L and in the group III 627 pmol/L (p = 0.206376 for the groups I and II, p = 0.05929 for the groups I and III and p = 0.0797 for the groups II and III. In group I there were no differences found in the HE4 concentrations in the peritoneal fluid, depending on the stage, grade, the presence of neoplastic cells and the peritoneal dissemination. The HE4 marker concentrations in the peritoneal fluid are highly irrespective of the pathology observed in the female sexual organ. Therefore, it seems that its determinations in the peritoneal fluid are completely useless in terms of diagnostics. More research is needed on the role of the HE4 marker, especially the place of its formation and possible use in the targeted therapy.
    Journal of Ovarian Research 02/2014; 7(1):22. · 2.43 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate human epididymis protein 4 (HE4) as an extrabiomarker to cancer antigen 125 (CA125) to improve the detection of ovarian carcinoma. METHODS: Sixty patients with ovarian carcinoma, 50 patients with benign ovarian tumors and 30 healthy women were included in the present study. Serum concentration of HE4 was assayed using ELISA technique, while CA125 was assayed using chemiluminescent enzyme immunoassay. RESULTS: The median CA125 and HE4 serum values were significantly higher among ovarian cancer patients when compared with healthy control However, the median serum levels of CA125 but not HE4 were significantly higher among patients with benign ovarian tumors as compared to healthy women. Based on the receiver operator characteristics curve analysis, HE4 had higher sensitivities than CA125 for the detection of ovarian cancer at 90, 95 and 98 % specificities and the combination of both markers yielded a higher sensitivity than either alone. However, CA125 but not HE4 had higher sensitivities for the detection of benign ovarian tumors at the same specificities. In addition, a positive correlation was observed between HE4 and CA125 among patients with ovarian carcinoma. CONCLUSION: HE4 is a valuable marker for ovarian cancer diagnosis and when combined with CA125, they had a higher sensitivity at a set specificity, thus providing a more accurate predictor of ovarian cancer than either alone.
    Archives of Gynecology 01/2013; · 0.91 Impact Factor


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