摘要
目的本实验探讨核糖核苷酸还原酶小亚基(RRM2)在上皮性卵巢癌中的表达及其与血管生成的关系。
方法采用免疫组化PV-6000二步法和半定量逆转录-聚合酶链反应(RT-PCR)技术,在15例正常卵巢组织、15例良性卵巢肿瘤组织、6例低度潜在恶性上皮性卵巢肿瘤组织和62例原发上皮性卵巢癌组织中检测RRM2、血管内皮细胞特异标记物-CD105(Endoglin)的表达及RRM2、CD105的mRNA表达量,用CD105标记微血管密度(MVD),分析RRM2mRNA和CD105mRNA表达的关系,并对患者进行术后生存情况随访,以研究两者表达与预后的关系。
结果(1)低度潜在恶性卵巢肿瘤组和上皮性卵巢癌组中的RRM2mRNA表达量(1.586±0.650,1.870±0.618)和蛋白阳性率(66.67%,69.35%),均高于正常卵巢组和良性卵巢肿瘤组中的RRM2mRNA表达量(0.771±0.495,0.952±0.601)和蛋白阳性率(0,26.67%)(P<0.05)；低度潜在恶性卵巢肿瘤组和上皮性卵巢癌组中的CD105mRNA表达量(2.190±0.512,2.735±0.636)和MVD计数(23.15±4.38,25.27±6.91),均高于正常卵巢组和良性卵巢肿瘤组中的CD105mRNA表达量(0.686±0.637,0.763±0.547)和MVD计数(3.40±1.78,12.15±2.29)(P<0.05)。(2)RRM2mRNA表达量和蛋白阳性表达率在FIGOⅢ-Ⅳ期高于Ⅰ-Ⅱ期(t=-2.370,χ2=5.937,P<0.05); CD105mRNA表达量和MVD计数与临床病理分期、癌组织分化程度和淋巴结转移有关。(3)RRM2mRNA和CD105mRNA之间表达成正相关(r=0.713,P<0.05)。(4)对卵巢癌患者术后生存的随访资料进行分析,Kaplan-Meier法比较生存曲线表明,RRM2阳性表达者术后生存时间短(P<0.05),COX多因素生存分析表明RRM2mRNA高水平表达者的死亡危险度是低水平表达者的2.378倍,RRM2是上皮性卵巢癌预后的独立影响因素。
结论(1)RRM2有望成为一个新的卵巢肿瘤诊断和判断预后的指标。(2)RRM2可能参与了卵巢癌的新生血管形成。(3)RRM2对上皮性卵巢癌患者的预后评估具有一定的指导意义
Objective:To investigate the role of RRM2 in the Epithelian Ovarian Cancer and its relation to tumor vascularization.
Methods:The mRNA and protein levels of RRM2 and CD105 in 98 ovarian specimens(including 15 normal,15 benign,6 borderline and 62 malignant) were detected with reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry. Microvessel density (MVD) was counted by endothelial cells immunostained with anti-CD105 monoclonal antibody.The relationship between the expressions of two genes was analyzed. The survival time after operation was followed up.
Results:(1) The mRNA levels (1.586±0.650,1.870±0.618)and protein positive rates(66.67%,69.35%) of RRM2 in borderline ovarian neoplasms and ovarian cancers wereand were both higher than that in normal group and benign group(0.771±0.495,0.952±0.601and 0,26.67%)(P<0.05); the mRNA levels(2.190±0.512, 2.735±0.636) and MVD(23.15±4.38,25.27±6.91) of CD 105 in borderline ovarian neoplasms and ovarian cancers were both higher than that in normal group and benign group(0.686±0.637,0.763±0.547 and 3.40±1.78,12.15±2.29)(P<0.05).(2) The mRNA levels and positive rates of RRM2 were higher in clinical stageⅢ～Ⅳthan that in stageⅠ～Ⅱ(t=-2.370,χ2=5.937,P<0.05); the mRNA levels and MVD of CD105 were associated with FIGO stage, grades of cytology differentiation, and the presence of lymph node metastasis(P<0.05).(3)Expression of RRM2mRNA was positively correlated with CD105mRNA expression in ovarian cancer tissues (r=0.713, P<0.05). (4) Kaplan-Meier method showed that patients survived shorter when ovarian cancer tissues showed higher positive rates of RRM2 (P<0.05);COX proportional risk model analysis indicated that the risk of mortality with high level of RRM2mRNA is 2.378 times as large as that with low.
Conclusion:(1) RRM2 maybe another new tumor marker for the diagnosis and judging prognosis in epithelical ovarian cancer. (2) RRM2 may be associated with the angiogenesis of epithelian ovarian cancer. (3) RRM2 may be another new tumor marker for predicting the prognosis in epithelical ovarian cancer.
引文
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