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[目的]探讨甲状腺癌患者血液中DNA甲基化情况,筛选出与甲状腺癌相关的甲基化分子标志物。[方法]收集上海地区14例甲状腺癌患者血液样本,10份正常对照血液样本,利用Illumina 27K甲基化芯片检测全血基因组DNA样本,得到甲状腺癌血液DNA甲基化谱,采用Fisher、Pearson和Wilcoxon检验等进行统计学和生物信息学分析。[结果]经病例组和对照组之间位点的甲基化差异分析,统计学筛选阈值选择P≤5×10-4时,29个基因在病例组中显著高表达(高甲基化);11个基因在病例组中低表达(低甲基化)。统计学筛选阈值选择P≤1×10-4时,则筛选出的差异甲基化基因(位点)总计8个,其中7个基因在病例组中显著高表达(高甲基化);1个基因在病例组中显著低表达(低甲基化)。构建甲状腺癌疾病诊断预测模型,在阈值为P≤1×10-4时筛选出来的8个差异甲基化基因对于疾病预测平均准确度达91.67%。[结论]血液中甲基化修饰异常的基因与甲状腺癌的发生发展有关,其有可能成为甲状腺癌血液诊断的分子标志物。
[Objective] To investigate the DNA methylation in the blood of patients with thyroid cancer and to screen out the methylation molecular markers associated with thyroid cancer. [Methods] The blood DNA of 14 patients with thyroid cancer and 10 normal control blood samples from Shanghai area were collected. Genomic DNA samples of whole blood were detected by Illumina 27K methylation chip to obtain DNA methylation profile of thyroid cancer. Fisher, Pearson and Wilcoxon test and other statistical and bioinformatic analysis. [Results] The results of methylation analysis showed that 29 genes were highly expressed (hypermethylated) in case group when P <5 × 10-4 was chosen as statistical threshold. The genes were low (hypomethylated) in the case group. When the statistical screening threshold is less than or equal to 1 × 10-4, a total of 8 differentially methylated genes (loci) were screened out, of which 7 genes were highly expressed (hypermethylated) in the case group and 1 gene Significantly low expression (hypomethylation) in the case group. To construct a predictive model of thyroid cancer, eight differential methylated genes screened out at a threshold of P≤1 × 10-4 had an average accuracy of 91.67% for disease prediction. [Conclusion] The abnormal gene methylation in blood is related to the occurrence and development of thyroid cancer, which may become a molecular marker for the diagnosis of thyroid cancer.