卵巢上皮性癌组织中DNA甲基转移酶亚型mRNA的表达及其意义

Expression of DNA methyltransferase 1, 3A and 3B mRNA in the epithelial ovarian carcinoma

目的探讨DNA甲基转移酶(DNMT)亚型mRNA在卵巢上皮性癌组织中的表达及其临床意义。方法采用半定量RT-PCR技术测定55例卵巢上皮性癌组织(其中原发性40例、复发性15例)及20例正常卵巢组织中DNMT亚型1、3A及3B mRNA的表达水平,并对其相关临床病理指标进行分析。结果正常卵巢、原发性及复发性卵巢上皮性癌组织中,DNMT1mRNA的表达水平分别为1.15、3.11、2.85,3者之间比较,差异有统计学意义(P<0.05);DNMT3A mRNA的表达水平分别为1.32、0.71、1.24,3者之间比较,差异无统计学意义(P>0.05);DNMT3B mRNA表达水平分别为0.25、0.60、2.12,复发性卵巢上皮性癌组织显著高于其他两者(P<0.01)。原发性卵巢上皮性癌组织中DNMT1mRNA表达水平,中低分化、手术病理分期为Ⅲ～Ⅳ期、淋巴结转移阳性者明显高于高分化、Ⅰ～Ⅱ期及淋巴结转移阴性者(分别为4.92和1.38,6.02和2.13,8.25和2.40;P均<0.05)。原发性卵巢上皮性癌组织中,浆液性癌和透明细胞癌组织中DNMT1、3A、3B mRNA表达水平(分别为5.64、1.00、0.78)均明显高于其他病理类型(分别为1.76、0.44、0.23;P均<0.05)。COX回归分析发现,卵巢上皮性癌组织中DNMT3B mRNA表达水平可能是影响患者生存期的惟一因素。结论原发性及复发性卵巢上皮性癌组织中,DNMT1、3B mRNA高表达与其疾病进展及预后有关。

Objective To explore the role of DNA methyltransferases （DNMT）1, 3A, 3B in the development of epithelial ovarian carcinoma. Methods Semi-quantitative RT-PCR method was used to detect the mRNA levels of DNMT 1,3A and 3B in the tissues of epithelial ovarian carcinoma from 55 cancer patients（40 primary and 15 recurrent cancer） and 20 normal ovary tissues, and the relevant clinical pathological parameters were analyzed. Results DNMT1 mRNA levels were 1.15,3.11,2. 85 ,respectively in normal ovary, primary and recurrent ovarian epithelial cancer tissues, with significant difference between them （P〈 0. 05 ）. DNMT3A mRNA levels had no obvious changes in the different groups, being 1.32, 0. 71,1.24, respectively （ P 〉 0. 05 ）. DNMT3B mRNA levels were 0. 25,0. 60,2. 12, in normal ovary, primary and recurrent ovarian epithelial cancer tissues, respectively and there was a significant increase in recurrent cancer tissues compared with normal and primary ovary cancer tissues（ P 〈 0. 01 ）. In the primary ovarian cancer tissues, DNMT1 mRNA levels were over expressed in the tissues of low-moderate differentiated （4. 92,1.38 ）, stage Ⅲ-Ⅳ （ 6.02,2.13 ） and lymphatic metastasis （ 8.25,2.40 ; P 〈 0. 05 ）. DNMT 1,3A, 3B mRNA were over expressed in primary carcinoma, serous carcinoma and clear cell carcinoma of the ovary （ 5.64,1.00,0. 78 ） , in comparison with the other pathologic types （ 1.76,0. 44, 0. 23 ） , the differences were significant （ P 〈 0. 05 ）. Using COX regression analysis, and after analyzing the parameters effecting survival in epithelial ovarian cancer tissues, including DNMT1,3A ,3B mRNA level and pathologic type, differentiation, surgical staging, lymphatic metastasis as well as residue tumor post cytoreductive surgery, we found that the mRNA level of DNMT3B was the only factor affecting survival of ovarian cancer patients. Conclusion DNMT1,3B mRNA were overexpressed in primary and recurrent epithelial ovarian carcinoma, and they have some correlation with clinical pathology and prognosis of epithelial ovarian carcinoma.