甲状腺癌患者血DNA甲基化分子标志物
Blood DNA Methylation Markers for Thyroid Cancer
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摘要:
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& #215;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& #215;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& #215;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。 Abstract:Objective To identify DNA methylation markers in blood samples of thyroid cancer patients. Methods Blood samples from 14 thyroid cancer patients and 10 healthy volunteers were collected in Shanghai. Genomic DNA samples were detected with Illumina Infinium Human Methylation 27K BeadChip for thyroid cancer blood DNA methylation profiles. Fisher, Pearson and Wilcoxon tests were used in statistical and bioinformatic analysis. Results In comparison of methylation between the case and control groups, 40 differentially methylated genes (29 high methylated genes and 11 low methylated genes) were identified if the statistic threshold was set to P ≤ 5& #215;10-4; however, 8 differentially methylated genes (7 high methylated genes and 1 low methylated gene) were identified if P ≤ 1& #215;10-4. The latter suggested better ability to diagnose thyroid cancer with the average accuracy of 91.67% in the thyroid cancer diagnosis model. Conclusion Aberrant methylated genes play an important role in tumorigenesis and could act as molecular markers to diagnosis thyroid cancer in blood.
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