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A protein and mRNA expression-based classification of gastric cancer.

基于蛋白质和mRNA表达的胃癌分类

Setia N,Agoston AT,Han HS,Mullen JT,Duda DG,Clark JW,Deshpande V,Mino-Kenudson M,Srivastava A,Lennerz JK,Hong TS,Kwak EL,Lauwers GY

Abstract

The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques.

摘要

尽管对已知的危险因素和随访措施改进不少,但胃癌患者的总生存率仍然很差。这凸显了新分类、并指导识别潜在的治疗靶点的需求。通过先进的分子技术和分析方法,三个部门(癌症基因组图谱、“新加坡公爵”研究小组和亚洲癌症研究组)最近提出了胃癌的遗传和表观遗传学分子分类。根据这些分类,我们研究了146例胃腺癌的14种生物标记物的表达,并使用不太昂贵的、可广泛使用的免疫组织化学和原位杂交法进行了无监督分层聚类分析。

最终,我们根据Epstein-Barr病毒(EBV)阳性、微卫星不稳定性、E-cadherin和p53的表达异常,确定了五组胃癌分型;其余病例的构成特点是p53表达正常。

另外,我们报道了五类分子亚型对应的临床病理学特征。我们还利用Cox比例风险模型进一步评价了这些分组与生存之间的关系,结果表明EBV相关和微卫星不稳定型腺癌患者中具有生存率较高的趋势。

总之,我们提出建议通过一个简单的检测、那就是使用免疫组化和原位杂交技术能够简单重现最近提出的胃癌分子分类。

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