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目的在肺癌的发生发展过程中,甲基化异常是导致相关基因失活的重要机制。本研究探讨肺癌患者谷胱甘肽S转移酶P1基因(Glutathione S-transferases P1,GSTP1)甲基化水平及其对肺癌诊断的临床价值。方法收集2015-10-01-2016-01-31郑州大学第一附属医院收治的100例患者的肺泡灌洗液,其中80例肺癌患者(小细胞肺癌和非小细胞肺癌)为肺癌组,20例良性肺疾病患者(肺炎、慢性阻塞性肺疾病和肺结核)为对照组。以PCR联合高分辨率熔解曲线(high resolution melting assay,HRM)(PCR-HRM)方法检测GSTP1基因启动子甲基化水平,并结合肺癌患者临床病理特征进行分析。结果肺癌组GSTP1基因启动子甲基化率为42.5%(34/80),显著高于对照组的15.0%(3/20),χ~2=5.191,P=0.023。不同年龄、性别及病理类型肺癌患者GSTP1基因启动子甲基化率,差异均无统计学意义,P值分别为0.397、0.853和0.751。早期(Ⅰ和Ⅱ期)肺癌患者GSTP1基因启动子甲基化率42.5%(17/40),显著低于晚期(Ⅲ和Ⅳ期)的70.0%(28/40),χ~2=11.931,P=0.013;但显著高于对照组,χ~2=4.538,P=0.033。高、中分化肺癌患者GSTP1基因启动子甲基化率为43.9%(18/41),显著低于低分化患者的79.5%(31/39),χ~2=10.664,P=0.010;但显著高于对照组,χ~2=4.974,P=0.026。结论 GSTP1基因启动子甲基化改变与肺癌发生发展及恶性程度有关,GSTP1基因启动子甲基化检测可能有助于肺癌诊断。
Objective In the development of lung cancer, abnormal methylation is an important mechanism leading to inactivation of related genes. This study was aimed to investigate the methylation level of Glutathione S-transferases P1 (GSTP1) and its clinical value in the diagnosis of lung cancer. Methods Totally 100 patients with bronchoalveolar lavage fluid were admitted to the First Affiliated Hospital of Zhengzhou University from October 2015 to January 2016, including 80 lung cancer patients (small cell lung cancer and non-small cell lung cancer) Cases of patients with benign lung disease (pneumonia, chronic obstructive pulmonary disease and tuberculosis) as the control group. The promoter methylation of GSTP1 gene was detected by polymerase chain reaction (PCR) combined with high-resolution melting assay (HRM), and the clinicopathological characteristics of patients with lung cancer were analyzed. Results The promoter methylation rate of GSTP1 gene was 42.5% (34/80) in lung cancer group, which was significantly higher than that in control group (15.0%, χ ~ 2 = 5.191, P = 0.023). The methylation rates of GSTP1 gene promoter in lung cancer patients of different age, gender and pathological type had no statistical significance, with P values of 0.397, 0.853 and 0.751 respectively. The promoter methylation rate of GSTP1 gene was 42.5% (17/40) in patients with stage Ⅰ and Ⅱ lung cancer, which was significantly lower than 70.0% (28/40) in stage Ⅲ and Ⅳ (χ ~ 2 = 11.931) P = 0.013; but significantly higher than the control group, χ ~ 2 = 4.538, P = 0.033. The promoter methylation rate of GSTP1 gene in high and moderately differentiated lung cancer patients was 43.9% (18/41), significantly lower than 79.5% (31/39) in poorly differentiated patients (χ ~ 2 = 10.664, P = 0.010) Higher than the control group, χ ~ 2 = 4.974, P = 0.026. Conclusions The methylation of GSTP1 promoter is related to the occurrence and progression of lung cancer. The detection of GSTP1 promoter methylation may contribute to the diagnosis of lung cancer.