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Overexpression of catalytic subunit M2 in patients with ovarian cancer 被引量:2

Overexpression of catalytic subunit M2 in patients with ovarian cancer
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摘要 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 Ill-IV presented higher RRM2 gene expression than those in clinical FIGO-stages I-I1. 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. Conclusion 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. 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 Ill-IV presented higher RRM2 gene expression than those in clinical FIGO-stages I-I1. 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. Conclusion 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.
出处 《Chinese Medical Journal》 SCIE CAS CSCD 2012年第12期2151-2156,共6页 中华医学杂志(英文版)
关键词 ovarian neoplasms ribonucleotide reductase M2 real-time quantitative polymerase chain reaction IMMUNOHISTOCHEMISTRY DIAGNOSIS PROGNOSIS ovarian neoplasms ribonucleotide reductase M2 real-time quantitative polymerase chain reaction immunohistochemistry diagnosis prognosis
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  • 1Lee Y, Vassilakos A, Feng N, et al. GTI-2040, an antisense agent targeting the small subunit component (R2) of human ribonucleotide reductase, shows potent antitumor activity against a variety of tumors.Cancer Res,2003, 63:2802-2811.
  • 2Fan H, Villegas C, Huang A, et al. The mammalian ribonucleotide reductase R2 component cooperates with a variety of oncogenes in mechanisms of cellular transformation.Cancer Res,1998,58:1650-1653.
  • 3Kuschak TI, Kuschak BC, Taylor CL, et al. c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene.Oncogene,2002,21:909-920.
  • 4Fredriksson JM, Nedergaard J. Norepinephrine specifically stimulates ribonucleotide reductase subunit R2 gene expression in proliferating brown adipocytes: mediation via a cAMP/PKA pathway involving Src and Erk1/2 kinases.Exp Cell Res,2002,274:207-215.

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