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通过全基因组表达谱分析发现和验证胃癌的预后标志物。

Discovery and validation of prognostic markers in gastric cancer by genome-wide expression profiling.

机构信息

Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.

出版信息

World J Gastroenterol. 2011 Apr 7;17(13):1710-7. doi: 10.3748/wjg.v17.i13.1710.

Abstract

AIM

To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis.

METHODS

Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we analyzed the expression of 47,296 transcripts in two batches of gastric cancer patients who underwent surgical resection. Thirty-nine samples in the first batch were used as the training set to discover candidate markers correlated to overall survival, and thirty-three samples in the second batch were used for validation.

RESULTS

A panel of ten genes were identified as prognostic marker in the first batch samples and classified patients into a low- and a high-risk group with significantly different survival times (P = 0.000047). This prognostic marker was then verified in an independent validation sample batch (P = 0.0009). By comparing with the traditional Tumor-node-metastasis (TNM) staging system, this ten-gene prognostic marker showed consistent prognosis results. It was the only independent prognostic value by multivariate Cox regression analysis (P = 0.007). Interestingly, six of these ten genes are ribosomal proteins, suggesting a possible association between the deregulation of ribosome related gene expression and the poor prognosis.

CONCLUSION

A ten-gene marker correlated with overall prognosis, including 6 ribosomal proteins, was identified and verified, which may complement the predictive value of TNM staging system.

摘要

目的

基于全基因组表达分析,开发一种能够预测患者总生存状态的预后基因集。

方法

使用 Illumina HumanWG-6 BeadChip 并进行半监督分析,我们分析了两批接受手术切除的胃癌患者的 47296 个转录本的表达。第一批中的 39 个样本被用作训练集,以发现与总生存相关的候选标记物,第二批中的 33 个样本用于验证。

结果

在第一批样本中,一组十个基因被确定为预后标记物,并将患者分为低风险和高风险组,生存时间有显著差异(P = 0.000047)。该预后标记物随后在独立的验证样本批次中得到验证(P = 0.0009)。与传统的肿瘤-淋巴结-转移(TNM)分期系统相比,该十基因预后标记物显示出一致的预后结果。它是多变量 Cox 回归分析的唯一独立预后价值(P = 0.007)。有趣的是,这十个基因中有六个是核糖体蛋白,这表明核糖体相关基因表达的失调与预后不良之间可能存在关联。

结论

鉴定并验证了与总预后相关的十个基因标记物,其中包括 6 个核糖体蛋白,这可能补充了 TNM 分期系统的预测价值。

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