组织和血浆cfDNA中HOXA6和HOXA7基因的异常甲基化在肺癌诊断中的作用

Role of Aberrant Methylation of HOXA6 and HOXA7 Genes in Tissue and Plasma cfDNA in the Diagnosis of Lung Cancer

DNA高甲基化是肿瘤抑制基因失活的重要机制,也是各种类型癌症早期诊断的生物标志物。本研究旨在揭示组织和血浆cfDNA中HOXA6和HOXA7基因的异常甲基化在肺癌诊断中的作用。2016年1月至2018年3月期间,收集54例非小细胞肺癌(NSCLC)患者作为研究对象,另外选择50名健康志愿者作为对照。检测受试者组织和血浆cfDNA中HOXA6和HOXA7基因甲基化阳性率,结果发现,NSCLC患者血浆cfDNA中的HOXA6甲基化率(40.74%)显著高于健康体检者(6.00%);NSCLC患者血浆cfDNA中的HOXA7甲基化率(35.19%)显著高于健康体检者(2.00%)。TNM分期为Ⅰ~Ⅱ期的患者的血浆cfDNA中HOXA6和HOXA7甲基化率均显著低于Ⅲ~Ⅳ期患者(p<0.05)。NSCLC患者肿瘤组织中的HOXA6和HOXA7甲基化率显著高于癌旁组织(p<0.05)。Spearman相关分析显示,血浆cfDNA和肿瘤组织中HOXA6基因甲基化的相关系数为r=0.834,p<0.001;血浆cfDNA和肿瘤组织中HOXA7基因甲基化的相关系数为r=0.882,p<0.001。血浆cfDNA中HOXA6和HOXA7基因异常甲基化诊断非小细胞肺癌的特异度分别为94.00%和98.00%。本研究表明,血浆cfDNA中HOXA6和HOXA7基因异常甲基化在诊断非小细胞肺癌中具有较高的特异度,并且可反映患者的疾病严重程度。

DNA hypermethylation is an important mechanism for the inactivation of tumor suppressor genes and a biomarker for the early diagnosis of various types of cancer.This study aimed to reveal the role of aberrant methylation of HOXA6 and HOXA7 genes in tissue and plasma cfDNA in the diagnosis of lung cancer.From January 2016 to March 2018,54 patients with non-small cell lung cancer(NSCLC)admitted to our hospital were selected as subjects,and 50 healthy volunteers were selected as controls.After detecting the positive methylation rate of HOXA6 and HOXA7 genes in the tissue and plasma cfDNA of the subjects,the HOXA6 methylation rate in the cfDNA of the NSCLC patients(40.74%)was significantly higher than that of the healthy subjects(6.00%).The rate of HOXA7 methylation in plasma cfDNA of patients with NSCLC(35.19%)was significantly higher than that of healthy subjects(2.00%).The methylation rates of HOXA6 and HOXA7 in plasma cfDNA of patients with TNM stageⅠ~Ⅱwere significantly lower than those of stageⅢ~Ⅳpatients(p<0.05).The methylation rate of HOXA6 and HOXA7 in tumor tissues of NSCLC patients was significantly higher than that in adjacent tissues(p<0.05).Spearman correlation analysis showed that the correlation coefficient of HOXA6 gene methylation between plasma cfDNA and tumor tissues was r=0.834,p<0.001;the correlation coefficient of HOXA7 gene methylation between plasma cfDNA and tumor tissues was r=0.882,p<0.001.The specificity of the abnormal methylation of HOXA6 and HOXA7 genes in plasma cfDNA for the diagnosis of non-small cell lung cancer was 94.00%and 98.00%,respectively.It is indicated that the abnormal methylation of HOXA6 and HOXA7 genes in plasma cfDNA has high specificity in the diagnosis of non-small cell lung cancer,and can reflect the severity of the disease.