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非小细胞肺癌患者中1型半胱氨酸双加氧酶启动子高甲基化

Promoter hypermethylation of cysteine dioxygenase type 1 in patients with non-small cell lung cancer.

作者信息

Yin Wei, Wang Xiang, Li Yunping, Wang Bin, Song Mingzhe, Hulbert Alicia, Chen Chen, Yu Fenglei

机构信息

Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.

Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.

出版信息

Oncol Lett. 2020 Jul;20(1):967-973. doi: 10.3892/ol.2020.11592. Epub 2020 May 6.

Abstract

In the present study, promoter hypermethylation of cysteine dioxygenase type 1 (CDO1) was evaluated in non-small cell lung cancer (NSCLC) tissues to assess the value of CDO1 as a novel biomarker to improve the diagnosis of NSCLC. Tumor tissue samples and corresponding normal lung tissue samples from 42 patients with NSCLC were obtained at the Department of Thoracic Surgery, The Second Xiangya Hospital (Changsha, China). Conventional methylation-specific PCR (cMSP) and methylation-on-beads followed by quantitative methylation-specific PCR (MOB-qMSP) were used to analyze the tumor and normal lung tissue samples. Using these two methods, promoter DNA hypermethylation of the CDO1 gene was detected in 59.4 and 71.0% of tumor tissues of patients with NSCLC and in 9.4 and 0% of normal lung tissue, respectively. Compared with the rate of methylation in the well-differentiated NSCLC tissues (15.4 and 55.6%, respectively), the rate of CDO1 gene promoter methylation was higher in the poorly differentiated tissues (89.5 and 92.3%, respectively). Overall, it was demonstrated that the MOB-qMSP method had a higher positive detection rate for CDO1 hypermethylation compared with the cMSP method. In conclusion, CDO1 gene promoter hypermethylation was more frequently observed in NSCLC tissues compared with in normal lung tissues, and a high methylation frequency of the CDO1 gene in biopsy specimens of NSCLC was associated with the degree of differentiation.

摘要

在本研究中,对非小细胞肺癌(NSCLC)组织中1型半胱氨酸双加氧酶(CDO1)的启动子高甲基化进行了评估,以评估CDO1作为改善NSCLC诊断的新型生物标志物的价值。从湘雅二医院胸外科(中国长沙)获取了42例NSCLC患者的肿瘤组织样本和相应的正常肺组织样本。采用常规甲基化特异性PCR(cMSP)和磁珠甲基化后定量甲基化特异性PCR(MOB-qMSP)分析肿瘤和正常肺组织样本。使用这两种方法,在NSCLC患者的肿瘤组织中分别有59.4%和71.0%检测到CDO1基因的启动子DNA高甲基化,而在正常肺组织中的检测率分别为9.4%和0%。与高分化NSCLC组织中的甲基化率(分别为15.4%和55.6%)相比,低分化组织中CDO1基因启动子甲基化率更高(分别为89.5%和92.3%)。总体而言,结果表明与cMSP方法相比,MOB-qMSP方法对CDO1高甲基化的阳性检测率更高。总之,与正常肺组织相比,NSCLC组织中更常观察到CDO1基因启动子高甲基化,且NSCLC活检标本中CDO1基因的高甲基化频率与分化程度相关。

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