DNA甲基转移酶1在胃癌组织中的表达及意义

Expression of DNA methyltransferase 1 in human gastric cancer tissue and its significance

目的探讨DNA甲基转移酶1(DNMTl)在胃癌中的表达及其与胃癌临床分期、分化程度及淋巴结转移等的关系。方法采用半定量逆转录-聚合酶链反应(RT-PCR)检测34例原发性胃癌患者癌组织及癌旁正常组织中DNMT1 mRNA的表达,采用免疫组级化学方法检测DNMT1蛋白的表达情况。结果正常组织和胃癌组织中均表达DNMT1 mRNA,胃癌组织中的相对含量为0.76±0.11,显著高于正常组织的0.45±0.14(P<0.05)。高、中分化胃癌组织中的DNMT1 mRNA相对含量为0.58±0.14,显著低于低、未分化胃癌组织的0.94±0.16(P<0.05)。不同性别、有无淋巴结转移、不同临床分期、不同肿瘤大小的胃癌组织间DNMT1 mRNA相对含量的差异均无统计学意义(P值均>0.05)。胃癌组织的DNMT1蛋白的表达程度显著高于正常组织(x^2= 7.760,P<0.01)。细胞分化程度低的癌组织DNMT1蛋白表达程度显著高于分化程度高的癌组织(x^2=4.500,P<0.05)。不同性别、有无淋巴结转移、不同临床分期、不同肿瘤大小的胃癌组织间DNMT1蛋白表达程度的差异均无统计学意义(x^2=0.09、1.270、1.830、0.30,P值均>0.05)。结论DNMT1的高表达是胃癌发生过程中的早期分子事件,是胃癌早期诊断及治疗的重要靶点。

Objective To study the expression of DNA methyltransferase 1 （DNMT1） in gastric cancer and its relationship with the clinical staging, differentiation degree, and lymphatic metastasis of gastric cancer. Methods The expression of DNMT1 mRNA was detected by semi quantitative Reverse Transcriptase Polymerase Chain Reaction （RT-PCR） in the cancer tissues and corresponding adjacent normal tissues in 34 gastric cancer patients. Immunohistochemistry was used to detect DNMT1 protein expression. Results DNMT1 mRNA was positive in both normal tissues and gastric cancer tissues; expression in gastric cancer tissue significantly was higher than that in normal tissues （0.76 ± 0.11 vs 0. 45 ＋ 0.14, P 〈 0.05）. DNMT1 mRNA expression in well and moderately diffe rentiated cancer cells was significantly lower than those of poorly and non differentiated cancer cells（0.58 ± 0. 14 vs 0. 94 ± 0.16, P 〈 0.05）, but the expression was not associated with gender, lymph node metastasis, clinical stage, and tumor size（P〉 0.05）. Immunohistochemistry showed the expression of DNMT1 protein in the cancer specimens was higher than that in the adjacent normal specimens（P 〈 0. 01） ; the expression in poorly differentiated cancer tissues was significantly higher than that of well differentiated cancer cells（P 〈0.05）; and the expression was not relationship with the size, gender, lymph node metastasis and clinical stage （all P 〉 0.05）. Conclusion Over-expression of DNMT1 is an early event of gastric cancer, and may serve as a indicator for early diagnosis and a target for therapy.