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目的探索5-羟甲基胞嘧啶(5-hmC)在结肠腺瘤癌变早期诊断中的应用。方法收集结肠腺瘤组织(轻度异型增生组,n=24)、结肠原位癌组织(重度异型增生组,n=24)及瘤/癌旁正常组织(对照)标本,检测特定靶向DNA序列(修复基因h MLH1片段)的5-hmC和5-甲基胞嘧啶(5-mC)含量。结果与对照组织相比,重度异型增生组与轻度异型增生组组织中5-hmC的相对含量均出现了不同程度的下降,且重度异型增生组较轻度异型组下降更明显,差异具有统计学意义(Z=-4.455,P<0.01)。5-hmC相对含量<0.165时,预测结肠腺瘤重度异型增生(原位癌)的灵敏度为62%,特异度为92%(AUC=0.125,P<0.01)。重度异型增生组与轻度异型增生组中5-mC的相对含量均表现出明显上升,但组间差异无统计学意义(Z=-1.454,P>0.05)。结论结肠腺瘤轻度异型增生发展为重度异型增生(原位癌)的过程中,组织中修复基因h MLH1片段的5-hmC含量逐渐减少是结肠腺瘤癌变的早期指标,5-hmC有望成为结肠腺瘤癌变早期诊断的潜在标志物。
Objective To explore the application of 5-hydroxymethylcytosine (5-hmC) in the early diagnosis of colon adenoma. Methods Colonic adenomas (mild dysplasia group, n = 24), colorectal carcinoma (severe dysplasia group, n = 24) and normal / paracancerous tissues (control) were collected to detect specific target DNA 5-hmC and 5-methylcytosine (5-mC) content of the sequence (repair gene h MLH1 fragment). Results Compared with the control group, the relative content of 5-hmC in severe dysplasia group and mild dysplasia group all decreased to some extent, and the severe dysplasia group was more obvious than the mild dysplasia group, the difference was statistically significant Significance (Z = -4.455, P <0.01). When the relative content of 5-hmC was less than 0.165, the sensitivity and specificity of predicting severe dysplasia (carcinoma in situ) of colorectal adenoma were 62% and 92% (AUC = 0.125, P <0.01). The relative content of 5-mC in severe dysplasia group and mild dysplasia group showed a significant increase, but there was no significant difference between groups (Z = -1.454, P> 0.05). Conclusions In the process of mild dysplasia of colorectal adenoma developing to severe dysplasia (carcinoma in situ), the decrease of 5-hmC content of hMLH1 fragment in the tissue is an early indicator of colorectal adenoma carcinogenesis, and 5-hmC is expected to become Potential markers of early diagnosis of colorectal adenoma.