Department of Obstetrics and Gynecology, Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong 266003, China.
Chin Med J (Engl). 2012 Jun;125(12):2151-6.
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.
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.
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.
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.
肿瘤的形成和生长与 DNA 的合成有关。核苷酸还原酶（RR）是一种调节 DNA 合成总速率的酶，因此在细胞生长中起着关键作用。催化亚基 M2（RRM2）是调节核苷酸还原酶酶活性的主要单位。本研究旨在探讨卵巢癌患者中 RRM2mRNA 和蛋白的表达及其与患者诊断和临床结局的关系。
采用免疫组织化学和实时定量聚合酶链反应（PCR）检测 98 例卵巢标本中 RRM2mRNA 水平和蛋白表达。分析 RRM2 蛋白的表达及其与临床病理特征的相关性。采用 Kaplan-Meier 检验评估 RRM2 表达与进展时间和生存的关系。采用 Cox 比例模型分析患者预后的危险因素。
上皮性卵巢癌患者中 43 例（69.4%）、交界性肿瘤患者中 10 例（66.7%）、良性肿瘤患者中 4 例（26.7%）、正常组中均未见 RRM2 免疫染色阳性。上皮性卵巢癌（1.722±0.639）和交界性卵巢肿瘤（1.365±0.615）中 RRM2mRNA 水平明显高于正常组（0.678±0.446）和良性组（0.828±0.545）。FIGO 分期为 III-IV 期的卵巢癌患者 RRM2 基因表达高于FIGO 分期为 I-II 期的患者。此外，低 RRM2mRNA 水平患者的生存明显好于高 RRM2mRNA 水平患者（P<0.05）。Cox 比例风险模型分析显示，高 RRM2mRNA 表达患者的死亡风险是低表达患者的 2.553 倍。
RRM2 表达与卵巢肿瘤的发生密切相关，可能成为诊断和预后疾病的新的预测标志物。
