食管癌高发区LINE-1甲基化与食管癌临床特征的关系
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摘要
目的探讨长散在重复序列(long interspersed nucleotide element-1,LINE-1)启动子区DNA甲基化水平与食管癌发生的关系。方法采用甲基化特异性上述聚合酶链式反应(polymerase chain reaction,PCR)和焦磷酸测序法检测96例食管癌组织、癌旁组织和远癌组织标本中LINE-1基因甲基化水平,并用统计学方法分析LINE-1甲基化与食管癌临床特征及吸烟等生活习惯的关系。结果 96例癌组织、癌旁组织和远癌组织中LINE-1甲基化水平差异均无统计学意义(均有P>0.05)。LINE-1启动子区甲基化与食管癌患者的年龄、饮酒、家族史、病理组织类型、肿瘤部位及临床病理分期之间差异均无统计学意义(均有P>0.05);与患者性别、吸烟和分化程度之间差异均有统计学意义(均有P<0.05)。结论 LINE-1启动子区甲基化在食管癌患者中较为普遍,LINE-1启动子区低甲基化常发生于食管癌低分化组织和TNM晚期,LINE-1基因甲基化有潜力在食管癌诊断和预后监测方面发挥重要作用。
Objective To study the function of long interspersed nucleotide element-1(LINE-1) promoter region methylation in the development of esophageal cancer. Methods Pyrosequencing was applied to detect methylation levels of the promoter region of LINE-1 in 96 cases of esophageal cancer tissuses, pericancerous tissue and tissues distant from esophageal cancer. Statistical methods were performed to correlate the level of LINE-1 methylation with clinical features and living habits of the patients. Results The methylation level of LINE-1 was not significantly different among the esophageal cancer tissuses, pericancerous tissue and tissues distant from esophageal cancer(all P>0.05). Among 96 cancer tissuses, no association was found between methylation status of LINE-1 promoter region and age, drinking, family history, histopathological types, tumor locaton and tumor stage(all P>0.05). Metylation status of LINE-1 promoter region was associated with gender, smoking history and tumor differentiation(all P<0.05). Conclusion The methylation of LINE-1 is frequently happened to esophageal cancer. Promoter region hypermethylation of LINE-1 is often occurred to poor differentiated esophageal cancer and advanced TNM stage. The methylation of LINE-1 may play an important role in the diagnosis and prognosis monitoring of esophageal cancer.
Objective To study the function of long interspersed nucleotide element-1(LINE-1) promoter region methylation in the development of esophageal cancer. Methods Pyrosequencing was applied to detect methylation levels of the promoter region of LINE-1 in 96 cases of esophageal cancer tissuses, pericancerous tissue and tissues distant from esophageal cancer. Statistical methods were performed to correlate the level of LINE-1 methylation with clinical features and living habits of the patients. Results The methylation level of LINE-1 was not significantly different among the esophageal cancer tissuses, pericancerous tissue and tissues distant from esophageal cancer(all P>0.05). Among 96 cancer tissuses, no association was found between methylation status of LINE-1 promoter region and age, drinking, family history, histopathological types, tumor locaton and tumor stage(all P>0.05). Metylation status of LINE-1 promoter region was associated with gender, smoking history and tumor differentiation(all P<0.05). Conclusion The methylation of LINE-1 is frequently happened to esophageal cancer. Promoter region hypermethylation of LINE-1 is often occurred to poor differentiated esophageal cancer and advanced TNM stage. The methylation of LINE-1 may play an important role in the diagnosis and prognosis monitoring of esophageal cancer.
引文
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[9] 杨建洲,纪爱芳,王金胜,等.太行山地区食管癌高发区人群血浆叶酸水平与食管鳞癌关系的研究 [J].中华内科杂志,2016,55(4):317-319.Yang JZ,Ji AF,Wang JS,et al.Correlationship between folate levels and esophageal cancer in the Taihang moutains living in a high-incidengce area [J].Chin J Intern Med,2016,55(4):317-319.DOI:10.3760/cma.j.issn.0578-1462.
[10] Hoshimoto S,Takeuchi H,Ono S,et al.Genome-wide hypomethylation and specific tumor-related gene hypermethylation are associated with esophageal squamous cell carcinoma outcome [J].J Thorac Oncol.2015,10(3):509-517.DOI:10.1097/JTO.0000000000000441.
[11] Kaneko K,Murakamii Y,Katagiri.Does daily alcohol and /or cigaratte consumption cause low-grade dysplasia,a precursor of esophageal squamous cell carcinoma outcome [J].J Clin Gas,2010,44(3):173-179.DOI:10.1097/MCG.0b013e3181bb83 7a.
[2] Barchitta M,Quattrocchi A,Maugeri A,et al.LINE-1 hypomethylation in blood and tissue samples as an epigenetic marker for cancer risk:a systematic review and meta-analysis [J].PLoS One,2014,9(10):e109478.DOI:10.1371/journal.pone.0109478.
[3] Doucet-O’Hare TT,Sharma R,Rodi'c N,et al.Somatically acquired LINE-1 insertions in normal esophagus undergo clonal expansion in esophageal squamous cell carcinoma [J].Hum Mutat.2016,37(9):942-954.DOI:10.1002/humu.23027.
[4] Baba Y,Watanabe M,Murata A,et al.LINE-1 hypomethylation,DNA copy number alterations,and CDK6 amplification in esophageal squamous cell carcinoma [J].Clin Cancer Res,2014,20(5):1114-1124.DOI:10.1158/1078-0432.
[5] 常江,繆小平.基因-环境交互作用与疾病风险预测模型研究进展 [J].中华疾病控制杂志,2018,22(4):323-325.Chang J,Miu XP.Gene-environment analysis in the study of chronic non-communicable diseases [J].Chin J Dis Control Prev,2018,22(4):323-325.DOI:10.16462/j.cnki.zhjbkz.2018.04.001.
[6] Baba Y,Huttenhower C,Nosho K,et al.Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors [J].Mol Cancer,2010,9:125-142.DOI:10.1186/1476-4598-9-125.
[7] Llanos AA,Marian C,Brasky TM,et al.Associations between genetic variation in onecarbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues in histologically normal breast tissues [J].Epigenetics,2015,10(8):727-735.DOI:10.1080/15592294.2015.1062205.
[8] Iwagami S,Baba Y,Watanabe M,et al.Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma [J].Ann Surg Oncol,2012,19(8):2726-2732.DOI:10.1245/s10434-011-2176-3.
[9] 杨建洲,纪爱芳,王金胜,等.太行山地区食管癌高发区人群血浆叶酸水平与食管鳞癌关系的研究 [J].中华内科杂志,2016,55(4):317-319.Yang JZ,Ji AF,Wang JS,et al.Correlationship between folate levels and esophageal cancer in the Taihang moutains living in a high-incidengce area [J].Chin J Intern Med,2016,55(4):317-319.DOI:10.3760/cma.j.issn.0578-1462.
[10] Hoshimoto S,Takeuchi H,Ono S,et al.Genome-wide hypomethylation and specific tumor-related gene hypermethylation are associated with esophageal squamous cell carcinoma outcome [J].J Thorac Oncol.2015,10(3):509-517.DOI:10.1097/JTO.0000000000000441.
[11] Kaneko K,Murakamii Y,Katagiri.Does daily alcohol and /or cigaratte consumption cause low-grade dysplasia,a precursor of esophageal squamous cell carcinoma outcome [J].J Clin Gas,2010,44(3):173-179.DOI:10.1097/MCG.0b013e3181bb83 7a.