Xiaohong Wang1, Yiqiang Liu2, Duanfang Shao3, Ziliang Qian4, Zhengwei Dong4, Yun Sun4, Xiaofang Xing3, Xiaojing Cheng3, Hong Du3, Ying Hu1, Yingai Li1, Lin Li3, Bin Dong2, Ziyu Li3, Aiwen Wu3, Xiaojiang Wu3, Zhaode Bu3, Xianglong Zong3, Guanshan Zhu4, Qunsheng Ji4, Xian-zi Wen5, Lian-hai Zhang6, Jia-fu Ji7. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Tissue Bank, Peking University Cancer Hospital and Institute, Beijing, 100142, China. 2. Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, China. 3. Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China. 4. Asia and Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, 201203, China. 5. Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China. 13661176007@163.com. 6. Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China. zlhzlh@hotmail.com. 7. Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China. jiafuj@gmail.com.
Abstract
BACKGROUND: Gastric cancer (GC) is an aggressive malignancy whose mechanisms of development and progression are poorly understood. The identification of prognosis-related genomic loci and genes may suffer from the relatively small case numbers and a lack of systematic validation in previous studies. METHODS: Array-based comparative genomic hybridization (aCGH) coupled with patient clinical information was applied to identify prognosis-related loci and genes with high-frequency recurrent gains in 129 GC patients. The candidate loci and genes were then validated using an independent cohort of 384 patients through branched DNA signal amplification analysis (QuantiGene assays). RESULTS: In the 129 patients, a copy number gain of three chromosome regions-namely, 8q22 (including ESRP1 and CCNE2), 8q24 (including MYC and TNFRSF11B), and 20q11-q13 (including SRC, MMP9, and CSE1L)--conferred poor survival for patients. In addition, the correlation between the branched DNA signal amplification analysis results and the aCGH results was analyzed in 73 of these 129 patients, and MYC, TNFRSF11B, ESRP1, CSE1L, and MMP9 were found to be well correlated. Further validation using an independent cohort (n = 384) verified that only MYC and TNFRSF11B within 8q24 are related to survival. Patients with gains in both MYC and TNFRSF11B had poorer survival than those with no gains, particularly those with noncardia GC. Gains in both of these genes were also a significant independent prognostic indicator. CONCLUSIONS: Our results revealed that copy number gains in MYC and TNFRSF11B located at 8q24 are associated with survival in GC, particularly noncardia GC.
BACKGROUND:Gastric cancer (GC) is an aggressive malignancy whose mechanisms of development and progression are poorly understood. The identification of prognosis-related genomic loci and genes may suffer from the relatively small case numbers and a lack of systematic validation in previous studies. METHODS: Array-based comparative genomic hybridization (aCGH) coupled with patient clinical information was applied to identify prognosis-related loci and genes with high-frequency recurrent gains in 129 GC patients. The candidate loci and genes were then validated using an independent cohort of 384 patients through branched DNA signal amplification analysis (QuantiGene assays). RESULTS: In the 129 patients, a copy number gain of three chromosome regions-namely, 8q22 (including ESRP1 and CCNE2), 8q24 (including MYC and TNFRSF11B), and 20q11-q13 (including SRC, MMP9, and CSE1L)--conferred poor survival for patients. In addition, the correlation between the branched DNA signal amplification analysis results and the aCGH results was analyzed in 73 of these 129 patients, and MYC, TNFRSF11B, ESRP1, CSE1L, and MMP9 were found to be well correlated. Further validation using an independent cohort (n = 384) verified that only MYC and TNFRSF11B within 8q24 are related to survival. Patients with gains in both MYC and TNFRSF11B had poorer survival than those with no gains, particularly those with noncardia GC. Gains in both of these genes were also a significant independent prognostic indicator. CONCLUSIONS: Our results revealed that copy number gains in MYC and TNFRSF11B located at 8q24 are associated with survival in GC, particularly noncardia GC.
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