DNA启动子甲基化致ADAMTS9蛋白下调促进大肠癌病程进展  

ADAMTS9 protein downregulation induced by DNA promoter methylation could promote the progression of colorectal cancer

作　　者：王凤[1] 王睿[2] 王衍晶[1] 

机构地区：[1]大连医科大学附属第一医院检验科,辽宁大连116011 [2]沈阳医学院附属中心医院检验科,辽宁沈阳110024

出　　处：《中国癌症杂志》2015年第6期446-451,共6页China Oncology

摘　　要：背景与目的:大肠癌的发病率逐年递增。该研究旨在考察ADAMTS9蛋白水平及其启动子甲基化水平在大肠癌发病及病程进展中的意义。方法:采用甲基化特异性PCR法,检测162例大肠癌患者外周血来源DNA样本中ADAMTS9基因启动子甲基化水平;并应用酶联免疫吸附试验法检测162例大肠癌患者和150例健康体检者血浆ADAMTS9蛋白水平。结果:与健康人相比,大肠癌患者血浆中ADAMTS9蛋白水平明显降低[(65.25±9.70)μg vs(50.28±9.66)μg,P<0.001];162例大肠癌患者中有66例ADAMTS9基因启动子存在甲基化(40.7%);甲基化患者的血浆ADAMTS9蛋白水平显著降低(P<0.001),而ADAMTS9蛋白低表达患者的血样ADAMTS9基因甲基化水平显著升高(P=0.007);ADAMTS9甲基化与肿瘤大小(P=0.017)和肿瘤分化程度(P=0.029)密切相关,而ADAMTS9蛋白低表达与浸润深度(P=0.020)、淋巴结转移(P=0.019)和Dukes分期(P=0.002)密切相关。结论:在大肠癌中,由DNA启动子甲基化引起的ADAMTS9蛋白表达下调可能参与大肠癌的发病、侵袭转移、并促进病程进展。Background and purpose： The morbidity of colorectal cancer in China increased year by year. This study aimed to explore the signifi cance of ADAMTS9 protein levels and promoter methylation in colorectal cancer onset and progression. Methods： ADAMTS9 promoter methylation status was detected by methylation specifi c PCR method in 162 colorectal cancer patients＇ peripheral blood DNA samples; Plasmatic ADAMTS9 protein levels was detected by enzyme-linked immunosorbent assay method in 162 colorectal cancer patients and 150 healthy subjects. Results： Compared with healthy people, patients with colorectal cancer had a significant lower ADAMTS9 protein level in plasma [（65.25±9.70）μg vs（50.28±9.66）μg, P〈0.001]; ADAMTS9 gene promoter methylation was observed in 66 among 162 colorectal cancer patients（40.7%）; The plasma level of ADAMTS9 protein in patients with methylated ADAMTS9 gene had signifi cantly reduced（P〈0.001）, while the plasma level of ADAMTS9 protein in patients with low ADAMTS9 protein had signifi cantly increased（P=0.007）; ADAMTS9 methylation is closely related to tumor size（larger, P=0.017） and tumor differentiation degree（P=0.029）, ADAMTS9 protein low expression is closely related to invasion depth（P=0.020）, lymph node metastasis（P=0.019） and Dukes staging（P=0.002）.Conclusion： ADAMTS9 protein downregulation induced by DNA promoter methylation may be involved in the pathogenesis, invasion and metastasis, and promote the progression in colorectal cancer.

关 键 词：大肠癌 ADAMTS9 甲基化 血浆 

分 类 号：R735.34[医药卫生—肿瘤]