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

World Journal of Gastroenterology 2011年第13期17卷 1710-1717页

作者： Yue-Zheng Zhang Lian-Hai Zhang Yang Gao Chao-Hua Li Shu-Qinjia Ni Liu Feng Cheng De-Yun Niu William CS Cho Jia-Fu Ji Chang-Qing Zeng Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100029 China CAS Key Laboratory of Genome Sciences andInformation Chinese Academy of Sciences Beijing Institute ofGenomics Beijing 100029 China Graduate School of ChineseAcademy of Sciences Beijing 100049 China Key Labora-tory of Carcinogenesis and Translational Research (Ministry ofEducation) Department of Surgery Beijing Cancer Hospitaland Institute Peking University School of Oncology Beijing100142 China Department of Clinical Oncology QueenElizabeth Hospital Hong Kong China Laboratory of Cancer Genomics and Personalized Medicine Beijing Institute of Genomics ChineseAcademy of Sciences Beijing 100029 China

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 lowand 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.

关键词： Gastric cancer Gene expression profiling survival markers Prognosis Ribosomal proteins

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