Combined RASSF1A and RASSF2A Promoter Methylation Analysis as Diagnostic Biomarker for Bladder Cancer.
Combined RASSF1A and RASSF2A Promoter Methylation Analysis as Diagnostic Biomarker for Bladder Cancer.
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DOI：
10.1155/2012/701814
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Lautenschlaeger T
中科院分区：
文献类型：
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作者：
Meng W;Huebner A;Shabsigh A;Chakravarti A;Lautenschlaeger T
启动子超甲基化是一种被广泛研究的表观遗传事件，已知会影响基因表达水平，已被提出作为多种类型癌症的潜在生物标志物。需要临床诊断生物标志物来可靠地预测膀胱癌复发。本文采用甲基化特异性高分辨熔解（MS-HRM）分析法，对64例福尔马林固定石蜡包埋（FFPE）膀胱癌及癌旁正常组织中5个Ras相关家族成员（RASSF 1A、RASSF 2A、RASSF 4、RASSF 5和RASSF 6）的基因启动子甲基化进行了研究。结果显示，73%（30/41）的移行细胞癌、100%（3/3）的鳞状细胞癌和100%（4/4）的小细胞癌存在RASSF 1A或RASSF 2A基因启动子甲基化，而仅6%（1/16）的正常组织存在RASSF基因启动子甲基化。RASSF 1A或RASSF 2A基因启动子甲基化检测阳性为鉴别癌组织提供了77%的灵敏度和94%的特异性，曲线下面积为0.854，表明RASSF 1A和RASSF 2A基因的启动子甲基化分析有可能用作膀胱癌患者的复发生物标志物。
Promoter hypermethylation, a widely studied epigenetic event known to influence gene expression levels, has been proposed as a potential biomarker in multiple types of cancer. Clinical diagnostic biomarkers are needed for reliable prediction of bladder cancer recurrence. In this paper, DNA promoter methylation of five C-terminal Ras-association family members (RASSF1A, RASSF2A, RASSF4, RASSF5, and RASSF6) was studied in 64 formalin-fixed paraffin-embedded (FFPE) bladder cancer and normal adjacent tissues using methylation-specific high-resolution melting (MS-HRM) analysis. Results showed that 73% (30/41) of transitional cell carcinoma, 100% (3/3) of squamous cell carcinoma, and 100% (4/4) of small cell carcinoma demonstrated promoter methylation of the RASSF1A or RASSF2A gene, but only 6% (1/16) of normal tissues had promoter methylation of RASSF genes. Testing positive for hypermethylation of RASSF1A or RASSF2A promoter provided 77% sensitivity and 94% specificity for identification of cancer tissues with an area under the curve of 0.854, suggesting that promoter methylation analysis of RASSF1A and RASSF2A genes has potential for use as a recurrence biomarker for bladder cancer patients.