DNMT1和DNMT3a在结直肠癌中的表达、临床意义及相关性研究

Expression and clinical significance of DNMT1 and DNMT3a in colorctal cancer and its correlation study

目的探讨结直肠癌组织中DNA甲基转移酶-1(DNMT1)和DNA甲基转移酶-3a(DNMT3a)的表达、临床意义及相关性。方法选取河北北方学院附属第一医院2017年2月~2018年2月手术切除的结直肠癌(癌组)和癌旁正常组织(正常组)各50例。应用实时荧光定量逆转录聚合酶链反应(qRT-PCR)检测两组DNMT1 mRNA和DNMT3a m RNA的表达,应用免疫组织化学染色法检测两组DNMT1和DNMT3a蛋白的表达。同时收集患者的临床资料,分析二者的表达与临床病理特征间的关系。应用Spearman检验分析两种因子间的相关性。结果 qRTPCR结果显示:癌组中DNMT1 mRNA和DNMT3a mRNA的表达水平均明显高于正常组,差异均有统计学意义(均P <0.05)。免疫组织化学染色法结果显示,癌组中DNMT1和DNMT3a蛋白阳性表达率均明显高于正常组,差异均有统计学意义(均P <0.05);癌组中DNMT1和DNMT3a蛋白表达水平均与病变浸润程度、TNM分期、淋巴结转移及肝转移相关(均P <0.05),而与肿瘤大小、分化程度无关(均P> 0.05)。Spearman相关性分析结果显示,癌组织中DNMT1与DNMT3a呈明显正相关(r=0.455,P <0.05)。结论 DNMT1和DNMT3a的异常表达在结直肠癌的发生、发展中发挥重要作用,二者具有协同作用,均可作为结直肠癌早期诊断和治疗监测的潜在生物学指标。

Objective To explore the expression, clinical significance and correlation of DNA methyltransferase-1(DNMT1) and DNA methyltransferase-3 a(DNMT3 a) in human colorectal adenocarcinoma tissues. Methods Fifty specimens of colorectal adenocarcinoma tissues(cancer group) and 50 specimens of normal colorectal tissues(normal group) in the First Affiliated Hospital of Hebei North University from February 2017 to February 2018 were selected. The expression levels of DNMT1 m RNA and DNMT3 a m RNA were detected by reverse transcription quantitative real-time polymerase chain reaction(qRT-PCR), and the expression levels of DNMT1 and DNMT3 a protein were detected by immunohistochemistry technique. The clinical data was collected to analyze the relationship between their expression and clinicopathological characteristics. The correlation was analyzed by Spearman test. Results The qRT-PCR results showed that the expression level of DNMT1 mRNA and DNMT3 a mRNA in the cancer group were higher than those in the normal group, the differences were all statistically significant(all P < 0.05). The immunohistochemical staining results showed that the positive rates of DNMT1 and DNMT3 a protein in cancer group were higher than those in the normal group, the differences were statistically significant(all P < 0.05). The expression of DNMT1 and DNMT3 a protein in cancer group was correlated with the depth of tumor invasion, TNM stage, lymph node metastasis, and liver metastasis(all P < 0.05), which was not correlated with tumor size and degree of differentiation(all P > 0.05). Spearmen correlation analysis showed that there was significant positive correlation between DNMT1 and DNMT3 a in cancer tissues(r = 0.455, P < 0.05). Conclusion The abnormal expression of DNMT1 and DNMT3 a plays an important role in the occurrence and development of colorectal cancer, they have a synergistic effect, both can be used as potential biological indicators for early diagnosis and treatment monitoring of colorectal cancer.