Clinicopathological and prognostic significance of Bmi-1 expression in human cervical cancer

Abstract

Objective. To investigate the clinical significance of Bmi-1 expression as a prognostic marker for cervical cancer. Design. Retrospectively collected data from a population-based cohort. Setting. Jiangsu Province Hospital. Population. Eighty-eight women diagnosed with cervical carcinoma between 2000 and 2003. Methods. RT-PCR assay was performed to determine Bmi-1 mRNA expression in 18 cervical cancer and noncancerous tissue samples and immunohistochemistry to detect Bmi-1 protein expression in 88 cervical cancer samples. The correlation between Bmi-1 expression and clinicopathological factors was analyzed. Additionally, statistical analyses were applied to test for prognostic associations. RNA interference was used to downregulate Bmi-1 expression in a cervical cancer cell line (HeLa). In vitro cytotoxicity was measured by the methylthiazoletetrazolium and colony formation assays. Effects of Bmi-1 inhibition on in vivo growth of cancer cells was detected by the tumorigenicity assay. Cell cycle distribution and cell apoptosis were measured by flow cytometry. Main Outcome Measures. The levels of Bmi-1 mRNA and protein expression in tissues were evaluated by RT-PCR and Western Blot assays. Results. The level of Bmi-1 mRNA expression in cervical cancer tissues was significantly higher than that in corresponding noncancerous tissues. High Bmi-1 expression was significantly correlated with poor tumor differentiation, advanced International Federation of Gynecology and Obstetrics stage and positive lymph node metastasis. Patients with high Bmi-1 expression showed shorter overall survival than those with low expression. Univariate and multivariate analyses showed that high Bmi-1 expression was an independent prognostic factor. Conclusions.RNA interference-mediated Bmi-1 inhibition could inhibit in vitro and in vivo growth, enhance apoptosis and induce cell cycle arrest of cervical cancer cells. Bmi-1 might be an independent prognostic marker for cervical cancer patients. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.