Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer.
Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer.
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DOI：
10.1038/sj.bjc.6602636
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发表时间：
2005-06-20
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
虽然没有可靠的血清生物标志物用于胃癌患者的诊断和监测，但我们测试了检测胃癌患者血清甲基化变化的潜在诊断和预后价值。从60例确诊胃腺癌患者和22例年龄匹配的非癌对照患者的治疗前血清中提取DNA。通过定量甲基化特异性PCR （MethyLight）检测10个肿瘤相关基因（APC、E-cadherin、GSTP1、hMLH1、MGMT、p15、p16、SOCS1、TIMP3和tgf - β RII）的启动子超甲基化。胃癌患者血清DNA优先甲基化表现在APC（17%）、E-cadherin（13%）、hMLH1（41%）和TIMP3（17%）基因。此外，III/IV期患者血清中甲基化APC （P=0.08）、TIMP3 （P=0.005）和hMLH1 （P=0.03）浓度较高。总共有33名癌症患者（55%）在血清中检测到这四种标志物中的至少一种甲基化，而3名正常受试者在血清中检测到甲基化（特异性86%）。联合使用APC和E-cadherin甲基化标记确定了预后较差的癌症患者亚组（中位生存期3.3 vs 16.1个月，P=0.006）。这些结果表明，在胃癌患者血清中检测DNA甲基化可能具有诊断和治疗价值。
While there is no reliable serum biomarker for the diagnosis and monitoring of patients with gastric cancer, we tested the potential diagnostic and prognostic values of detecting methylation changes in the serum of gastric cancer patients. DNA was extracted from the pretherapeutic serum of 60 patients with confirmed gastric adenocarcinoma and 22 age-matched noncancer controls. Promoter hypermethylation in 10 tumour-related genes (APC, E-cadherin, GSTP1, hMLH1, MGMT, p15, p16, SOCS1, TIMP3 and TGF-beta RII) was determined by quantitative methylation-specific PCR (MethyLight). Preferential methylation in the serum DNA of gastric cancer patients was noted in APC (17%), E-cadherin (13%), hMLH1 (41%) and TIMP3 (17%) genes. Moreover, patients with stages III/IV diseases tended to have higher concentrations of methylated APC (P=0.08), TIMP3 (P=0.005) and hMLH1 (P=0.03) in the serum. In all, 33 cancers (55%) had methylation detected in the serum in at least one of these four markers, while three normal subjects had methylation detected in the serum (specificity 86%). The combined use of APC and E-cadherin methylation markers identified a subgroup of cancer patients with worse prognosis (median survival 3.3 vs 16.1 months, P=0.006). These results suggest that the detection of DNA methylation in the serum may carry both diagnostic and therapeutic values in gastric cancer patients.
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影响因子：
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