title: Overexpression of catalytic subunit M2 in patients with ovarian cancer.
abstract: BACKGROUND
  The formation and growth of tumors are related to the synthesis of the DNA. The enzyme ribonucleotide reductase (RR) is an enzyme that regulates the total rate of DNA synthesis and thus plays a pivotal role in cell growth. Catalytic subunit M2 (RRM2) is the main unit modulating the ribonucleotide reductase enzymatic activity. This study aimed to investigate the expression of RRM2 mRNA and protein in patients with ovarian cancer and its relevance to diagnosis and clinical outcome of the patients.
  
  
  METHODS
  RRM2 mRNA levels and protein expression were detected in 98 ovarian specimens with immunohistochemistry and real-time quantitative polymerase chain reaction (PCR). Expression of the RRM2 protein and correlation of the RRM2 gene expression with clinical pathological features were analyzed. The Kaplan-Meier test was used for evaluating RRM2 expression and time to progression and survival. The Cox proportional model was used to analyze the risk factors in prognosis of patients.
  
  
  RESULTS
  Positive RRM2 immunostaining was found in 43 of 62 (69.4%) patients with epithelial ovarian cancer, 10 of 15 (66.7%) patients with borderline neoplasm, 4 of 15 (26.7%) patients with benign growths, and none of the normal group. The RRM2 mRNA levels were significantly over expressed in epithelial ovarian cancer (1.722 ± 0.639) and borderline ovarian neoplasms (1.365 ± 0.615), compared to the normal group (0.678 ± 0.446) and benign group (0.828 ± 0.545). Patients with ovarian caner in clinical FIGO-stages III-IV presented higher RRM2 gene expression than those in clinical FIGO-stages I-II. Furthermore, the survival of patients with low RRM2 mRNA level was significantly better than patients with high levels (P < 0.05). By Cox proportional risk model analysis, the risk of mortality of patients with high level expression of RRM2 mRNA was 2.553 times greater than those with low expression.
  
  
  CONCLUSIONS
  RRM2 expression closely correlates with the development of ovarian tumor and may serve as a novel predictive marker for diagnosis and prognosis of the disease.
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong 266003, China. wlmqingyi@163.com
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wang
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Lu
authors.forename: Shao-Yan
authors.initials: SY
authors.lastname: Zhang
authors.forename: Ru-Yong
authors.initials: RY
authors.lastname: Yao
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xing
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Wei
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase