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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血清中高甲基化的FAM5C和MYLK作为胃癌的诊断和预警标志物
DOI：
10.1155/2012/473251
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Liu, Bingya
中科院分区：
文献类型：
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作者：
Chen, Lu;Su, Liping;Liu, Bingya
大多数胃癌(GC)患者不能及早诊断，因此有必要寻找有效的生物标志物对其进行诊断和预警。我们已经使用甲基化DNA免疫沉淀(MeDIP)来识别在胃癌细胞系中频繁甲基化的基因。采用甲基化特异性聚合酶链式反应(MSP)检测58例胃癌、46例胃癌前病变和30例正常对照血清中候选基因启动子区的甲基化状态。通过阵列分析获得82个高甲基化基因，筛选出5个候选基因(BCAS4、CHRM2、FAM5C、PrAC和Mylk)。进一步证实有3个基因(CHRM2、FAM5C和Mylk)显示甲基化速率随着从NC到GPL再到GC的进程而增加。从术前到术后评估，FAM5C和Mylk高甲基化的检出明显减少，而CHRM2的检出无明显变化(P<；0.001)。FAM5C和Mylk基因甲基化联合检测对胃癌诊断和预警的敏感性(77.6%，45/58)和预警(30.4%，14/46)均高于单基因检测，特异性也高达90%。FAM5C和Mylk的联合甲基化状态与肿瘤大小(P<；0.001)、肿瘤侵袭深度(P=0.001)和肿瘤转移分期(P=0.003)相关。超甲基化的FAM5C和Mylk可作为胃癌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.