CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease
CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease
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DOI：
10.1002/ijc.25356
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发表时间：
2011-01-15
影响因子：
6.4
通讯作者：
Zhang, Yali
中科院分区：
文献类型：
--
作者：
Chen, Kequan;Wang, Guanghai;Zhang, Yali
细胞粘附分子1（CADM 1/TSLC 1）是一种参与细胞粘附、增殖和凋亡的肿瘤抑制因子，在多种肿瘤中由于启动子甲基化而失活。但CADM 1/TSLC 1在结直肠癌发生过程中的变化及其临床意义尚不清楚。本研究的目的是确定CADM 1/TSLC 1基因功能失活在结直肠肿瘤发生中的作用及其作为结直肠癌患者临床评估的新表观遗传标记的潜力。采用逆转录聚合酶链反应（RT-PCR）、免疫印迹（Western blot）和免疫组织化学方法检测了8株大肠癌细胞系、54例原发性大肠癌及其相应癌旁组织中CADM 1/TSLC 1的表达水平。通过亚硫酸氢盐基因组测序和甲基化特异性聚合酶链反应分析CADM 1/TSLC 1启动子甲基化状态，并评价其与临床病理特征的相关性。所有统计检验均为双侧。CADM 1/TSLC 1表达下调在7/8（88%）结直肠癌细胞系和39/54（72%）原发性结直肠癌中观察到。CADM 1/TSLC 1基因启动子区甲基化发生率为75%（6/8），59%（32/54），与进展期结直肠癌相关。CADM 1/TSLC 1基因的表观遗传失活是结直肠癌发生发展过程中的一种常见改变，可作为结直肠癌患者分子分期的潜在生物标志物。
Cell adhesion molecule 1 (CADM1/TSLC1), a putative tumor suppressor involving in cell adhesion, proliferation and apoptosis, is frequently inactivated in several carcinomas due to promoter hypermethylation. But alterations of CADM1/TSLC1 in colorectal carcinogenesis and clinical significance have not been elucidated yet. The aim of this study was to determine the role of functional inactivation of CADM1/TSLC1 gene in colorectal tumorigenesis and its potential as a novel epigenetic marker for clinical assessment of patients with colorectal cancer. We measured CADM1/TSLC1 expression levels in 8 colorectal cancer cell lines, 54 primary colorectal carcinomas and their corresponding non-cancerous tissues by reverse transcription polymerase chain reaction, western blot analysis and immunohistochemistry. We analyzed CADM1/TSLC1 promoter methylation status by bisulfite genomic sequencing and the methylation special polymerase chain reaction, and evaluated its correlation with clinicopathological characteristics. All statistical tests were 2-sides. Downregulation of CADM1/TSLC1 expression was observed in 7 of 8 (88%) colorectal cancer cell lines and in 39 of 54 (72%) primary colorectal carcinomas. Hypermethylation of CADM1/TSLC1 promoter region occurred in 6 of 8 (75%) colorectal cancer cell lines and 32 of 54 (59%) primary colorectal carcinomas, and was correlated with advanced colorectal carcinoma. Epigenetic inactivation of CADM1/TSLC1 gene is a frequent alteration in development of colorectal cancer and can be a potential biomarker for molecular staging of patients with colorectal cancer.