【摘要】 目的研究肺癌患者血浆Ras相关区域家族蛋白1A(RASSF1A)、矮小同源盒基因2(SHOX2)基因甲基化水平与肺癌侵袭转移的关系。方法选取2016年2月至2017年5月于该院就诊的96例肺癌患者为肺癌组(经组织病理学确诊);选取同期114例健康体检者作为对照组。亚硫酸氢钠处理基因组DNA后采用直接测序法检测血浆中RASSF1A、SHOX2基因甲基化水平;分析肺癌患者血浆RASSF1A、SHOX2基因甲基化与临床病理特征及预后的相关性;多因素COX回归分析影响肺癌预后的因素。结果肺癌组血浆RASSF1A、SHOX2基因甲基化阳性率高于对照组,差异有统计学意义(P<0.05);RASSF1A、SHOX2基因甲基化与肺癌患者年龄、性别、吸烟情况、肿瘤大小、病理类型无关(P>0.05),与肺癌患者组织分化程度、淋巴结转移、TNM分期有关(P<0.05);RASSF1A、SHOX2基因甲基化与肺癌患者预后有关(P<0.05),且RASSF1A、SHOX2甲基化组患者死亡比例高于RASSF1A、SHOX2非甲基化组;RASSF1A、SHOX2基因甲基化、TNM分期是影响肺癌患者死亡的独立危险因素(P<0.05)。结论 RASSF1A、SHOX2基因甲基化可能在肺癌侵袭转移过程中发挥重要作用,为肺癌预后评估提供了重要依据,并有可能为其基因治疗提供新的靶点。更多还原

【Abstract】 Objective To investigate the correlation between the methylation levels of Ras association domain family protein 1 A(RASSF1 A) and short stature homobox 2(SHOX2) genes in plasma of patients with lung cancer, and its correlation with the invasion and metastasis of lung cancer.Methods A total of 96 patients with lung cancer who were treated in our hospital from February 2016 to May 2017 were enrolled as lung cancer group, at the same time, the other 114 healthy subjects who underwent physical examination were enrolled as control group. The methylation levels of RASSF1 A and SHOX2 genes in plasma were detected by direct sequencing after DNA was treated by sodium bisulfite. The correlation between methylation of RASSF1 A, SHOX2 genes and the clinicopathological features as well as the prognosis of patients was analyzed. The influencing factors on the prognosis of patients were analyzed by multivariate COX regression.Results The methylation positive rates of RASSF1 A and SHOX2 genes in lung cancer group were significantly higher than those in control group(P<0.05). The methylation of RASSF1 A and SHOX2 genes were not related with patient’s age and gender, smoking, tumor size and pathological type(P>0.05), which were related to the histological differentiation degree, lymph node metastasis and TNM stage(P<0.05). The methylations of RASSF1 A and SHOX2 gene were related to the prognosis of patients(P<0.05).Moreover the death rate in the RASSF1 A and SHOX2 methylation group was significantly higher than that in RASSF1 A and SHOX2 non methylation group. The methylation of RASSF1 A, SHOX2 gene and TNM stage were the independent risk factors of death of patients with lung cancer(P<0.05).Conclusion Methylation of RASSF1 A and SHOX2 genes may play an important role in the process of invasion and metastasis of lung cancer, which provides an important basis for prognosis evaluation of lung cancer, and a new target for gene therapy.更多还原