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胃癌中 hTERT 的甲基化与表达。

hTERT methylation and expression in gastric cancer.

机构信息

Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, SP, Brasil.

出版信息

Biomarkers. 2009 Dec;14(8):630-6. doi: 10.3109/13547500903225912.

Abstract

Gastric cancer is the second most prevalent cause of cancer death worldwide. DNA methylation is a common event in gastric carcinogenesis. hTERT seems to be the rate-limiting determinant of telomerase activation, which is responsible for stability and life span. hTERT hypermethylation has been associated with telomerase expression. In the present study, we investigated the promoter methylation status and hTERT protein expression in gastric cancer and normal mucosa samples. One hundred and nine gastric cancer and 53 normal mucosa samples were investigated through methylation-specific PCR. Immunohistochemistry was analysed using peroxidase in 55 gastric cancer and 18 normal gastric mucosa samples. This is the first study evaluating hTERT methylation status in gastric carcinogenesis. We did not observe hTERT protein expression in normal gastric mucosa. Moreover, hTERT expression was observed in 80% of tumours and was associated with gastric cancer (p < 0.0001). Partial methylation was the most frequent pattern in gastric samples, even in normal mucosa. The frequency of specimens presenting hypermethylation was significantly higher in tumours than in normal mucosa samples (p = 0.0002), although the presence of hypermethylated promoter was not associated with a higher frequency of hTERT expression. A low correlation between hTERT protein expression and methylation was verified in gastric cancer samples. There was a clear difference in the frequency of hTERT expression and methylation within tumoral and non-tumoral tissues. Methylation status and telomerase expression may be useful for the diagnosis of gastric cancer and may have an impact on the anti-telomerase strategy for cancer therapy.

摘要

胃癌是全球癌症死亡的第二大主要原因。DNA 甲基化是胃癌发生过程中的一个常见事件。hTERT 似乎是端粒酶激活的限速决定因素,端粒酶负责稳定性和寿命。hTERT 高甲基化与端粒酶表达有关。本研究通过甲基化特异性 PCR 检测了 109 例胃癌和 53 例正常胃黏膜样本的启动子甲基化状态和 hTERT 蛋白表达情况。通过过氧化物酶免疫组化分析了 55 例胃癌和 18 例正常胃黏膜样本的 hTERT 蛋白表达情况。这是首次评估 hTERT 甲基化状态在胃癌发生过程中的研究。我们在正常胃黏膜中未观察到 hTERT 蛋白表达。此外,在 80%的肿瘤中观察到 hTERT 表达,与胃癌相关(p < 0.0001)。部分甲基化是胃样本中最常见的模式,甚至在正常黏膜中也是如此。肿瘤样本中高甲基化标本的频率明显高于正常黏膜样本(p = 0.0002),尽管高甲基化启动子的存在与 hTERT 表达的频率增加无关。在胃癌样本中验证了 hTERT 蛋白表达与甲基化之间的低相关性。在肿瘤和非肿瘤组织中,hTERT 表达和甲基化的频率存在明显差异。甲基化状态和端粒酶表达可用于胃癌的诊断,并可能对癌症治疗的抗端粒酶策略产生影响。

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