Aberrant methylation of the PTPRO gene in peripheral blood as a potential biomarker in esophageal squamous cell carcinoma patients.
Aberrant methylation of the PTPRO gene in peripheral blood as a potential biomarker in esophageal squamous cell carcinoma patients.
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DOI：
10.1016/j.canlet.2011.08.032
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发表时间：
2012-02-28
期刊：
影响因子：
9.7
通讯作者：
Zhang, Hao
中科院分区：
文献类型：
--
作者：
You, Yan-Jie;Chen, Yu-Ping;Zheng, Xiao-Xuan;Meltzer, Stephen J.;Zhang, Hao
蛋白酪氨酸磷酸酶受体O型（PTPRO），PTP家族的一个新成员，通过超甲基化的失活已被描述在几种形式的癌症中。我们评估了PTPRO高甲基化作为食管鳞状细胞癌（ESCC）潜在的表观遗传学生物标志物。在36例原发性肿瘤中，27例（75%）观察到PTPRO高甲基化，并与浸润深度（T分期，P = 0.013）显著相关。在匹配的ESCC患者外周血样本中，13/36（36.1%）的血浆中可检测到甲基化PTPRO，15/36（41.7%）的血沉棕黄层中有甲基化PTPRO。在10名健康人的正常外周血样本中未观察到甲基化PTPRO。此外，通过5-aza-dC处理的去甲基化导致PTPRO甲基化和沉默的ESCC细胞系中的基因重新激活。这是第一个报告检测PTPRO作为一个非侵入性的生物标志物，在外周血中的实体瘤。我们的研究结果表明，高甲基化PTPRO发生在食管鳞癌频繁。在ESCC患者外周血中检测到它说明了它作为非侵入性诊断和疾病监测的表观遗传生物标志物的潜在临床应用。
Inactivation of protein tyrosine phosphatase receptor-type O (PTPRO), a new member of the PTP family, by hypermethylation has been described in several forms of cancers. We evaluated PTPRO hypermethylation as a potential epigenetic biomarker in esophageal squamous cell carcinoma (ESCC). PTPRO hypermethylation was observed in 27 (75%) of 36 primary tumors and correlated significantly with depth of invasion (T-stage, P = 0.013). Among matched peripheral blood samples from ESCC patients, 13 (36.1%) of 36 had detectable methylated PTPRO in plasma, and 15 (41.7%) of 36 had it in the buffy coat. No methylated PTPRO was observed in normal peripheral blood samples from 10 healthy individuals. In addition, demethylation by 5-aza-dC treatment led to gene reactivation in PTPRO-methylated and -silenced ESCC cell lines. This is the first report for detection of PTPRO as a non-invasive biomarker for solid tumors in peripheral blood. Our findings suggest that hypermethylated PTPRO occurs frequently in ESCC. Its detection in the peripheral blood of ESCC patients illustrates its potential clinical application as an epigenetic biomarker for noninvasive diagnosis and disease monitoring.
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