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Discovery and validation of prognostic markers in gastric cancer by genome-wide expression profiling
Yue-Zheng Zhang, Lian-Hai Zhang, Yang Gao, Chao-Hua Li, Shu-Qin Jia, Ni Liu, Feng Cheng, De-Yun Niu, William CS Cho, Jia-Fu Ji, Chang-Qing Zeng
Yue-Zheng Zhang, Yang Gao, Chao-Hua Li, Feng Cheng, De-Yun Niu, Chang-Qing Zeng, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China
Yue-Zheng Zhang, Yang Gao, Chao-Hua Li, Feng Cheng, De-Yun Niu, CAS Key Laboratory of Genome Sciences and Information, Chinese Academy of Sciences, Beijing Institute of Genomics, Beijing 100029, China
Yue-Zheng Zhang, De-Yun Niu, Graduate School of Chinese Academy of Sciences, Beijing 100049, China
Lian-Hai Zhang, Shu-Qin Jia, Ni Liu, Jia-Fu Ji, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Beijing Cancer Hospital and Institute, Peking University School of Oncology, Beijing 100142, China
William CS Cho, Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
Chang-Qing Zeng, Laboratory of Cancer Genomics and Personalized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China
Author contributions: Zhang YZ and Zhang LH contributed equally to this work; Ji JF and Zeng CQ are corresponding authors; Ji JF, Zhang LH, Gao Y and Zeng CQ contributed to the conception of this study; Gao Y, Zhang YZ, Zhang LH, and Ji JF designed the research strategy and experiments; Ji JF and Zhang LH collected samples and clinical data; Li CH, Zhang LH, Jia SQ, Zhang YZ, Liu N and Niu DY did sample preparation and chip array; Zhang YZ, Zhang LH, Gao Y and Cheng F did the data analysis and interpretation; Zhang YZ and Zhang LH prepared the manuscript; Zeng CQ, Ji JF and Cho WCS revised the manuscript.
Supported by the National 863 Program (SQ2009AA02XK1482570 and 2006AA02A402), Beijing Municipal Committee of Science and Technology (D0905001040631) and Beijing Capital Development Foundation of Health Bureau (2007-2051)
Correspondence to: Chang-Qing Zeng, Professor, Beijing Institute of Genomics, Chinese Academy of Sciences, Key Laboratory of Genome Sciences and Information, Chinese Academy of Sciences, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
czeng@big.ac.cn
Telephone: +86-10-82275720 Fax: +86-10-82275694
Received: September 27, 2010
Revised: November 3, 2010
Accepted: November 10, 2010
Published online: April 7, 2011
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.
