食管癌高发区LINE-1甲基化与食管癌临床特征的关系

崔国艳; 杨建洲; 陈云霞; 胡文庆; 王金胜

doi:10.16462/j.cnki.zhjbkz.2019.05.008

食管癌高发区LINE-1甲基化与食管癌临床特征的关系

doi: 10.16462/j.cnki.zhjbkz.2019.05.008

1.
046000 长治, 长治医学院微生物教研室
2.
046000 长治, 长治医学院公共卫生与预防教研室
3.
046000 长治, 长治医学院附属和济医院外科
4.
046000 长治, 长治医学院病理科

基金项目:

山西省回国留学人员科研资助项目 2014-072

山西省自然科学基金项目 2016011092

山西省"服务产业创新学科群建设计划"项目 201809

详细信息

通讯作者:
杨建洲, E-mail: jzyang@aliyun.com

中图分类号: R181
计量
- 文章访问数: 390
- HTML全文浏览量: 145
- PDF下载量: 49
- 被引次数: 0
出版历程
- 收稿日期: 2018-09-26
- 修回日期: 2019-03-01
- 刊出日期: 2019-05-10

Clinicopathological features of LINE-1 gene methylation with esophageal cancer in a high incidence area in China

1.
Department of Microbiology of Changzhi Medical College, Changzhi 046000, China
2.
Public Health and Preventive Medicine of Changzhi Medical College, Changzhi 046000, China
3.
Department of general surgery of Heping Hospital, Changzhi Medical College, Changzhi 046000, China
4.
Department of Changzhi Medical College, Changzhi 046000, China

Funds:

Research Project Supported by Shanxi Scholarship Council of China 2014-072

Natural Science Foundation of Shanxi Province of China 2016011092

Shanxi Province Service Industry Innovation Discipline group Construction Plan 201809

More Information

Corresponding author: YANG Jian-zhou, E-mail: jzyang@aliyun.com

摘要

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。
- 食管癌 /
- LINE-1基因 /
- 甲基化
Abstract: 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-1promoter 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.
- Esophageal cancer /
- LINE-1 gene /
- Methylation

HTML全文

图 1 癌组织、癌旁组织和远癌组织中LINE-1甲基化水平

Figure 1. Levels of LINE-1 methylation in cancer, paracancer and distal cancer tissues

下载: 全尺寸图片幻灯片

图 2 LINE-1基因的MSP电泳图

M：代表特异性甲基化引物扩增；U：代表特异性非甲基化引物扩增; N：代表远癌组织；P：代表癌旁组织；C：代表癌组织

Figure 2. Methylation-specific PCR of LINE-1 gene

下载: 全尺寸图片幻灯片

表 1 LINE-1甲基化与食管癌临床病理特征的关系

Table 1. Association between clinical charicteristics and methylation of LINE-1 in esphageal cancer patients

临床特征	例数(例)	光密度值(x±s)	P值
年龄(岁)			0.282
≤60	46	0.818±0.613
> 60	50	0.952±0.601
性别			0.007
男	48	0.724±0.498
女	48	1.052±0.666
吸烟情况			0.004
不吸烟	60	1.007±0.676
吸烟	36	0.689±0.409
饮酒			0.283
是	18	0.790±0.350
否	78	0.911±0.652
食管癌家族史			0.590
有	22	0.826±0.465
无	74	0.906±0.645
病理组织类型			0.491
鳞癌	78	0.867±0.586
腺癌	18	0.978±0.704
肿瘤部位			0.553
胸上段	48	0.870±0.571
胸中段	30	0.834±0.506
胸下段	16	1.026±0.836
分化程度			0.006
低分化	20	0.553±0.299
中分化	58	0.819±0.546
高分化	18	1.480±0.668
肿瘤TNM分期			0.065
Ⅰ期	35	1.101±0.653
Ⅱ期	8	0.801±0.384
Ⅲ期	40	0.787±0.550
Ⅳ期	13	0.677±0.653

下载: 导出CSV

参考文献(11)

[1]	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. DOI: 10.3322/caac.21338.
[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. doi: 10.16462/j.cnki.zhjbkz.2018.04.001 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. doi: 10.3760/cma.j.issn.0578-1462 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.0b013e3181bb837a.