非小细胞肺癌miRNA-191启动子区甲基化状态及其临床病理特征的相关分析

Analysis of relationship between methylation status of miRNA-191 promoter region and its clinicopathological characteristics in non-small cell lung cancer

目的探讨非小细胞肺癌(NSCLC)微小RNA(miRNA)-191启动子区甲基化状态及其在NSCLC发生、发展中的意义。方法甲基化特异性PCR(MSP)检测105份NSCLC患者术后肿瘤组织及其对应癌旁组织中的miRNA-191启动子甲基化水平,并分析miRNA-191启动子区甲基化状态与对应患者临床病理特征间的关系。结果105份NSCLC肿瘤标本中有48份发生甲基化,甲基化率为45.71%,对应的癌旁组织中有87份发生甲基化,甲基化率为82.86%,二者比较差异有统计学意义(χ2=37.87,P<0.01)。miRNA-191启动子区甲基化组与非甲基化组在TNM分期、肿瘤组织分化程度方面比较,差异有统计学意义(χ2=4.27、6.75,P=0.04、0.01),非甲基化组的TNM分期更晚、组织分化程度更低;而性别、年龄、组织类型方面比较,差异无统计学意义(χ2=0.01、0.89、1.80,P=0.91、0.35、0.25)。生存分析结果显示,与NSCLC患者甲基化组比较,NSCLC患者非甲基化组的总生存期更短(χ2=6.06,P=0.01)。结论NSCLC肿瘤组织miRNA-191的甲基化率明显低于癌旁组织,NSCLC的发生、发展过程可能与miRNA-191启动子区的异常甲基化密切相关。

Objective To investigate the methylation status of miRNA-191 promoter region in non-small cell lung cancer(NSCLC)and its significance in the occurrence and development of NSCLC.Methods The methylation-specific PCR(MSP)was used to detect the methylation level of miRNA-191 promoter in postoperative tumor tissues and corresponding paracancerous tissues of 105 patients with NSCLC,and to analyze the relationship between the methylation status of miRNA-191 promoter region and the clinicopathological characteristics of the corresponding patients.Results Among 105 tumor specimens of NSCLC,48 cases were methylated with a methylation rate of 45.71%,87 cases of the corresponding paracancerous tissues were methylated with a methylation rate of 82.86%,and the difference between the two groups was statistically significant(χ2=37.87,P<0.01).There were statistically significant differences in the TNM staging and tumor tissue differentiation between the miRNA-191 promoter methylation and non-methylation groups(χ2=4.27,6.75,P=0.04,0.01).The TNM stage in the non-methylated group was later and the degree of tissue differentiation was lower.There was no statistically significant difference in the gender,age and tissue type(χ2=0.01,0.89,1.80,P=0.91,0.35,0.25).The survival analysis results showed that compared with the methylated group of NSCLC patients,the overall survival period of the non-methylated group of NSCLC patients was shorter(χ2=6.06,P=0.01).Conclusion The methylation rate of miRNA-191 in NSCLC tumor tissues is significantly lower than that in paracancerous tissues,and the occurrence and development process of NSCLC may be closely related to the abnormal methylation in the promoter region of miRNA-191.