Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer

被引:0
作者
W K Leung
K-F To
E S H Chu
M W Y Chan
A H C Bai
E K W Ng
F K L Chan
J J Y Sung
机构
[1] The Chinese University of Hong Kong,Department of Medicine & Therapeutics
[2] Prince of Wales Hospital,Department of Anatomical & Cellular Pathology
[3] The Chinese University of Hong Kong,Department of Surgery
[4] Prince of Wales Hospital,undefined
[5] The Chinese University of Hong Kong,undefined
[6] Prince of Wales Hospital,undefined
来源
British Journal of Cancer | 2005年 / 92卷
关键词
gastric cancer; promoter hypermethylation; tumour suppressor genes; oncogenes;
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:2190 / 2194
页数:4
相关论文
共 162 条
[1]  
Eads CA(2000)MethyLight: a high-throughput assay to measure DNA methylation Nucleic Acids Res 28 E32-3418
[2]  
Danenberg KD(2001)Epigenetic patterns in the progression of esophageal adenocarcinoma Cancer Res 61 3410-463
[3]  
Kawakami K(2004)Epigenetics in human disease and prospects for epigenetic therapy Nature 429 457-641
[4]  
Saltz LB(2003)Profile of aberrant CpG island methylation along the multistep pathway of gastric carcinogenesis Lab Invest 83 635-1811
[5]  
Blake C(2000)Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma J Natl Cancer Inst 92 1805-186
[6]  
Shibata D(2004)Comparison of methylation-specific polymerase chain reaction (MSP) with reverse transcriptase–polymerase chain reaction (RT-PCR) in peripheral blood of gastric cancer patients J Surg Oncol 87 182-1766
[7]  
Danenberg PV(2002)Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma Clin Cancer Res 8 1761-2301
[8]  
Laird PW(2001)Concurrent hypermethylation of multiple tumor-related genes in gastric carcinoma and adjacent normal tissues Cancer 91 2294-7645
[9]  
Eads CA(2003)DNA methylation in serum of breast cancer patients: an independent prognostic marker Cancer Res 63 7641-211
[10]  
Lord RV(2001)Age-related hypermethylation of the hMLH1 promoter in gastric cancers Int J Cancer 94 208-228