Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma
Aberrant DNA methylation of PAX1, SOX1 and ZNF582 genes as potential biomarkers for esophageal squamous cell carcinoma
复制标题
PAX1、SOX1 和 ZNF582 基因的异常 DNA 甲基化作为食管鳞状细胞癌的潜在生物标志物
DOI：
10.1016/j.biopha.2019.109488
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发表时间：
2019-12-01
影响因子：
7.5
通讯作者：
Wang，Guo
中科院分区：
文献类型：
--
作者：
Tang，Li;Liou，Yu-Ligh;Wang，Guo
食管鳞状细胞癌（Esophageal squamous cell carcinoma，ESCC）是一种高度侵袭性的恶性肿瘤，大多数患者在诊断时已是晚期，预后差。为早期筛查ESCC鉴定敏感和特异的生物标志物是提高患者总体生存率的关键。（配对盒基因1），SOX 1（性别决定区Y-box-1）和ZNF 582结果食管鳞癌组织中PAX 1、SOX 1和ZNF 582基因甲基化水平均显著高于癌旁组织（P均<0. 0001）。PAX 1甲基化检测肿瘤的准确性、敏感性和特异性分别为0.754、96.0%和51.4%，SOX 1甲基化检测肿瘤的准确性、敏感性和特异性分别为0.781、89.2%和59.5%，ZNF 582甲基化检测肿瘤的准确性、敏感性和特异性分别为0.898、93.2%和75.7%。最重要的是，ZNF 582甲基化检测在女性ESCC患者中的敏感性和特异性均达到100%。PAX 1/SOX 1/ZNF 582基因甲基化是食管鳞癌发生的独立危险因素。女性患者肿瘤组织中ZNF 582甲基化水平高于男性患者，中、低分化肿瘤组织中ZNF 582甲基化水平高于高分化肿瘤组织。结论食管鳞癌组织中PAX 1、SOX 1和ZNF 582基因甲基化水平均高于癌旁组织和正常组织，提示PAX 1/SOX 1/ZNF 582甲基化检测可能成为食管鳞癌筛查和诊断的一个有前景的生物学指标。
BackgroundEsophageal squamous cell carcinoma (ESCC) is a highly invasive malignant tumor and the majority of patients have advanced stage of ESCC at diagnosis with poor outcome. Identification of sensitive and specific biomarkers for early screening of ESCC is critical for improving patient overall survival.MethodsPyrosequencing was used to determine the magnitude of DNA methylation on the selected regions PAX1 (paired box gene1), SOX1(sex determining region Y-box-1), and ZNF582 (zinc finger protein 582) in ESCC.ResultsThe methylation levels ofPAX1, SOX1, and ZNF582 genes were significantly higher in the cancerous tissues compared to those in the non-cancerous (all P < 0.0001). The accuracy, sensitivity and specificity of PAX1 methylation for the detection of cancer were respectively 0.754, 96.0% and 51.4%; for SOX1 which were 0.781, 89.2% and 59.5%; for ZNF582 which were 0.898, 93.2% and 75.7%. Most importantly, both the sensitivity and specificity of ZNF582 methylation testing achieved 100% in female ESCC patients. Hypermethylation of PAX1/SOX1/ZNF582 exhibited as an independent risk factor for ESCC development. In addition, ZNF582 methylation level in tumor tissue from the female patients was higher than that from male patients, and it was higher in the moderate and poor differentiated tumors compared to that in well-differentiated tumors. SOX1 methylation level was significantly higher in tumors located in the upper region than those located in the middle or lower regions.ConclusionThe methylation levels ofPAX1, SOX1 and ZNF582 genes were all higher in cancer tissues than in paired-adjacent and normal tissues, suggesting that detection of PAX1/SOX1/ZNF582 methylation status may serve as a promising biomarker for ESCC screening and diagnosis.
癌变期间印迹域的表观遗传反应。
影响因子：
5.7
作者：
Bretz CL;Langohr IM;Kim J
通讯作者：
Kim J