title: Detection of circulating Bmi-1 mRNA in plasma and its potential diagnostic and prognostic value for uterine cervical cancer.
abstract: Bmi-1 is overexpressed in uterine cervical cancer (UCC) and is found to be associated with adverse clinical characteristics and poor prognosis. However, little information is available on the status of circulating Bmi-1 mRNA in UCC. Because circulating cell-free nucleic acids have emerged as a novel class of markers for cancer detection, our research aims to address this question by detecting the circulating Bmi-1 mRNA and to assess its diagnostic and prognostic potential in UCC. Reverse transcription quantitative real-time PCR method was established to detect the circulating Bmi-1 mRNA in plasma of 109 patients with UCC, 138 patients with cervical intraepithelial neoplasia (CIN) and 80 healthy volunteers, and found that it was significantly increased in UCC compared with CINs and healthy controls (all at p < 0.001). Moreover, its high level was significantly correlated with advanced clinical stage (p < 0.001) and positive lymph nodes metastasis (p = 0.002). The area under the receiver operating characteristic curve (AUC) was 0.881, and the optimal cut-off value was 0.057, providing a sensitivity of 69.7% and a specificity of 95.9%. The AUC for circulating Bmi-1 mRNA showed higher diagnosis capability than that for SCC-Ag (p = 0.035) or CA125 (p < 0.001) currently utilized. Kaplan-Meier analysis demonstrated a correlation between increased circulating Bmi-1 mRNA level and reduced disease-free survival (DFS) (p = 0.001) and overall survival (OS) (p = 0.015). And, Cox analysis indicated that it was an independent prognostic factor for DFS and OS. We conclude that circulating Bmi-1 mRNA may be a potential noninvasive molecular marker for diagnosis and prognosis of UCC.
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Chuanxin
authors.initials: C
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Lutao
authors.initials: L
authors.lastname: Du
authors.forename: Shun
authors.initials: S
authors.lastname: Wang
authors.forename: Guixi
authors.initials: G
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xuewei
authors.initials: X
authors.lastname: Zhuang
authors.forename: Xuhua
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D024602:Glyceraldehyde-3-Phosphate Dehydrogenase (NADP+)(Phosphorylating) / Q000097:blood / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D009687:Nuclear Proteins / Q000235:genetics*; D020648:Peptide Elongation Factor 1 / Q000097:blood / Q000235:genetics; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood*; D012097:Repressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000097:blood* / Q000175:diagnosis / Q000235:genetics
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; C094814:EEF1A1 protein, human; D009687:Nuclear Proteins; D020648:Peptide Elongation Factor 1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D024602:Glyceraldehyde-3-Phosphate Dehydrogenase (NADP+)(Phosphorylating); D063150:Polycomb Repressive Complex 1