title: The expression of ribonucleotide reductase M2 in the carcinogenesis of uterine cervix and its relationship with clinicopathological characteristics and prognosis of cancer patients.
abstract: BACKGROUND
  To investigate the implication of ribonucleotide reductase M2 (RRM2) in the carcinogenesis of uterine cervix and its relationship with clinicopathological characteristics and prognosis of cancer patients.
  
  
  RESULTS
  The impact of RRM2 on cell viability was investigated in SiHa cervical cancer cells after RRM2 knockdown and the addition of cisplatin, which induces inter- and intra-strand DNA crosslinks. RRM2 immunoreactivity was evaluated by semi-quantitative H score among 29 normal, 30 low-grade dysplasia, 30 high-grade dysplasia and 103 invasive cancer tissue specimens of the uterine cervix, using tissue microarrays. RRM2 was then correlated with the clinicopathological variables of cervical cancer and patient survival. A greater toxic effect on cell viability using cisplatin was reflected by the greater reduction in RRM2 protein expression in SiHa cells. The RRM2 expression in cancer tissues was higher than that in high-grade dysplasia, low-grade dysplasia or normal cervical tissues. RRM2 upregulation was correlated with deep stromal invasion, large tumors and parametrial invasion and predicted poor survival.
  
  
  CONCLUSIONS
  RRM2 is a new molecular marker for the diagnosis and clinical outcomes of cervical cancer. It is involved in cervical carcinogenesis and predicts poor survival, and may be a potential therapeutic target including in cisplatin treatment.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Stomatology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Ying-Fang
authors.initials: YF
authors.lastname: Su
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Tzu-Fan
authors.initials: TF
authors.lastname: Wu
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Jiunn-Liang
authors.initials: JL
authors.lastname: Ko
authors.affiliation: School of Nursing, Chung Shan Medical University, Taichung, Taiwan; Department of Nursing, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Hsiu-Ting
authors.initials: HT
authors.lastname: Tsai
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Yi-Torng
authors.initials: YT
authors.lastname: Tee
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Wan Fan Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Cardiology, Department of Internal Medicine, Yuan-Sheng Hospital and Changhua Christian Hospital, Yuanlin Branch, Yuanlin, Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Chou
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Wea-Lung
authors.initials: WL
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Low
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ming-Yung
authors.initials: MY
authors.lastname: Chou
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*
chemical_list: C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase