title: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China. luomin_gz@yahoo.com.cn
authors.forename: Luo
authors.initials: L
authors.lastname: Min
authors.forename: Shen
authors.initials: S
authors.lastname: Dong-Xiang
authors.forename: Guo
authors.initials: G
authors.lastname: Xiao-Tong
authors.forename: Guan
authors.initials: G
authors.lastname: Ting
authors.forename: Chen
authors.initials: C
authors.lastname: Xiao-Dong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002681:China; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1