Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity.
Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity.
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DOI：
10.1158/1055-9965.epi-11-0548
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Cover TL
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文献类型：
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作者：
Loh JT;Shaffer CL;Piazuelo MB;Bravo LE;McClain MS;Correa P;Cover TL
幽门螺杆菌感染是胃癌发生的危险因素，而细菌癌蛋白CagA参与了胃癌的发生。我们分析了来自哥伦比亚人的幽门螺杆菌分离株，并观察到不同菌株在CagA表达水平上存在显著差异。为了阐明这种变异的基础，我们分析了每个菌株CagA翻译起始点上游的序列。CagA翻译起始点上游的DNA基序(AATAAGATA)与CagA的高水平表达有关。实验研究表明，该基序对于CagA的高水平表达是必要的，但不是充分的。来自哥伦比亚胃癌发病率较高地区的幽门螺杆菌菌株比来自胃癌发病率较低地区的菌株表达更高水平的CagA，而来自欧洲系统地理来源的哥伦比亚菌株比来自非洲的菌株表达更高水平的CagA。胃活检标本的组织病理学分析显示，与感染低水平CagA或缺乏AATAAGATA基序的菌株相比，高表达CagA或含有AATAAGATA基序的菌株与更晚期的癌前病变有关。不同幽门螺杆菌菌株间cagA表达差异很大。这项研究中发现的DNA基序与CagA的高水平表达有关，可能是预测胃癌风险的有用生物标志物。这些发现有助于解释为什么一些感染cagA阳性幽门螺杆菌的人会患上胃癌，而另一些人则不会。
Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis. We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression. To elucidate the basis for this variation, we analyzed sequences upstream from the CagA translational initiation site in each strain. A DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was associated with high levels of CagA expression. Experimental studies showed that this motif was necessary but not sufficient for high-level CagA expression. H. pylori strains from a region of Colombia with high gastric cancer rates expressed higher levels of CagA than did strains from a region with lower gastric cancer rates, and Colombian strains of European phylogeographic origin expressed higher levels of CagA than did strains of African origin. Histopathological analysis of gastric biopsy specimens revealed that strains expressing high levels of CagA or containing the AATAAGATA motif were associated with more advanced precancerous lesions than those found in persons infected with strains expressing low levels of CagA or lacking the AATAAGATA motif. CagA expression varies greatly among H. pylori strains. The DNA motif identified in this study is associated with high levels of CagA expression, and may be a useful biomarker to predict gastric cancer risk. These findings help to explain why some persons infected with cagA-positive H. pylori develop gastric cancer and others do not.