Hypermethylated FAM5C and MYLK in serum as diagnosis and pre-warning markers for gastric cancer.
Hypermethylated FAM5C and MYLK in serum as diagnosis and pre-warning markers for gastric cancer.
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DOI：
10.3233/dma-2011-0877
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Liu B
中科院分区：
文献类型：
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作者：
Chen L;Su L;Li J;Zheng Y;Yu B;Yu Y;Yan M;Gu Q;Zhu Z;Liu B
大多数胃癌（GC）病例在早期并不能被诊断出来，因此有必要寻找有效的生物标志物来诊断和预警。我们使用甲基化 DNA 免疫沉淀 (MeDIP) 来鉴定胃癌细胞系中经常甲基化的基因。通过甲基化特异性聚合酶链式反应（MSP）测试血清样本中候选基因的启动子区域高甲基化，包括GC（n = 58）、胃癌前期病变（GPL，n = 46）和正常对照（NC，n = 30）。通过芯片分析获得82个高甲基化基因，并选择5个基因（BCAS4、CHRM2、FAM5C、PRAC和MYLK）作为候选基因。进一步证实三个基因（CHRM2、FAM5C 和 MYLK）显示甲基化率随着从 NC 到 GPL、再到 GC 的进展而增加。从术前到术后评估，FAM5C 和 MYLK 高甲基化检测明显下降，但 CHRM2 没有下降 (P < 0.001)。 FAM5C和MYLK高甲基化联合检测比单一基因检测具有更高的GC诊断敏感性(77.6%,45/58)和预警(30.4%,14/46),且特异性高达90%。 FAM5C 和 MYLK 的联合高甲基化状态与肿瘤大小 (P < 0.001)、肿瘤浸润深度 (P = 0.001) 和肿瘤淋巴结转移 (TNM) 分期 (P = 0.003) 相关。高甲基化的FAM5C和MYLK可作为GC诊断和预警的潜在生物标志物。
Most cases of gastric cancer (GC) are not diagnosed at early stage which can be curable, so it is necessary to identify effective biomarkers for its diagnosis and pre-warning. We have used methylated DNA immunoprecipitation (MeDIP) to identify genes that are frequently methylated in gastric cancer cell lines. Promoter regions hypermethylation of candidate genes were tested by methylation-specific polymerase chain reaction (MSP) in serum samples, including GC (n = 58), gastric precancerous lesions (GPL, n = 46), and normal controls (NC, n = 30). Eighty two hypermethylated genes were acquired by array analysis and 5 genes (BCAS4, CHRM2, FAM5C, PRAC and MYLK) were selected as the candidate genes. Three genes (CHRM2, FAM5C and MYLK) were further confirmed to show methylation rates increased with progression from NC to GPL, then to GC. There was obvious decrease in detection of FAM5C and MYLK hypermethylation, but not CHRM2, from preoperative to postoperative evaluation (P < 0.001). Combined detection of FAM5C and MYLK hypermethylation had a higher sensitivity in GC diagnosis (77.6%,45/58) and pre-warning (30.4%,14/46) than one single gene detection and also had a high specificity of 90%. The combined hypermethylated status of FAM5C and MYLK correlated with tumor size (P < 0.001), tumor invasion depth (P = 0.001) and tumor-node-metastasis (TNM) stage (P = 0.003). Hypermethylated FAM5C and MYLK can be used as potential biomarkers for diagnosis and pre-warning of GC.