巴西北部人群胃腺癌中CDH1、FHIT、MTAP和PLAGL1的启动子高甲基化
Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil.
作者信息
Leal Mariana Ferreira, Lima Eleonidas Moura, Silva Patrícia Natália Oliveira, Assumpção Paulo Pimentel, Calcagno Danielle Queiroz, Payão Spencer Luiz Marques, Burbano Rommel Rodríguez, Smith Marília Arruda Cardoso
机构信息
Genetics Division, Department of Morphology, Federal University of São Paulo, São Paulo, SP, Brazil
出版信息
World J Gastroenterol. 2007 May 14;13(18):2568-74. doi: 10.3748/wjg.v13.i18.2568.
AIM
To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics.
METHODS
Methylation-specific PCR (MSP) assay was performed in 13 nonneoplastic gastric adenocarcinoma, 30 intestinal-type gastric adenocarcinoma and 35 diffuse-type gastric adenocarcinoma samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher's exact test to assess associations between methylation status and clinico-pathological characteristics.
RESULTS
Hypermethylation frequencies of CDH1, FHIT, MTAP and PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hypermethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hypermethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender.
CONCLUSION
Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.
目的
评估CDH1、FHIT、MTAP和PLAGL1启动子的甲基化状态，并探讨这些结果与临床病理特征的相关性。
方法
对来自巴西北部个体的13份非肿瘤性胃腺癌、30份肠型胃腺癌和35份弥漫型胃腺癌样本进行甲基化特异性PCR（MSP）检测。采用卡方检验或Fisher精确检验进行统计分析，以评估甲基化状态与临床病理特征之间的关联。
结果
CDH1、FHIT、MTAP和PLAGL1启动子的高甲基化频率分别为98.7%、53.9%、23.1%和29.5%。与非肿瘤性癌症相比，三个或四个基因的高甲基化与弥漫型胃癌显著相关。胃癌中较高的高甲基化频率与幽门螺杆菌感染显著相关，尤其是弥漫型。无淋巴结转移的癌症样本显示FHIT高甲基化频率更高。MTAP高甲基化与胃癌样本中的幽门螺杆菌有关，与肠型相比，也与弥漫型有关。在弥漫型中，MTAP高甲基化与女性性别有关。
结论
我们的研究结果显示肿瘤组织中存在差异基因甲基化，由此我们可以得出结论，高甲基化与胃癌发生有关。MTAP启动子高甲基化可被视为弥漫型胃癌的标志物，尤其是在女性中，可能有助于诊断、预后和治疗。44.9%的样本中存在幽门螺杆菌感染。这种感染可能通过基因启动子高甲基化与致癌过程相关，尤其是弥漫型中的MTAP启动子。弥漫型中较高的幽门螺杆菌感染可能是由于更大的遗传易感性。
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