Recurrent amplification of MYC and TNFRSF11B in 8q24 is associated with poor survival in patients with gastric cancer
Recurrent amplification of MYC and TNFRSF11B in 8q24 is associated with poor survival in patients with gastric cancer
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DOI：
10.1007/s10120-015-0467-2
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发表时间：
2016-01-01
期刊：
影响因子：
7.4
通讯作者：
Ji, Jia-fu
中科院分区：
文献类型：
--
作者：
Wang, Xiaohong;Liu, Yiqiang;Ji, Jia-fu
胃癌是一种侵袭性的恶性肿瘤，其发生和发展的机制尚不清楚。针对以往研究中病例数较少且缺乏系统性验证的问题，采用基于阵列的比较基因组杂交（aCGH）技术结合患者临床资料，对129例胃癌患者中复发率较高的复发相关基因位点和基因进行了鉴定。然后通过分支DNA信号扩增分析，使用384名患者的独立队列验证候选基因座和基因在129名患者中，三个染色体区域（即8 q22）的拷贝数增加，（包括ESRP 1和CCNE 2），8 q24（包括MYC和TNFRSF 11B）和20 q11-q13（包括SRC，MMP 9和CSE 1 L）的基因表达导致患者的生存率低下。另外，对这129例患者中的73例进行了分支DNA信号扩增分析结果与aCGH结果的相关性分析，发现MYC、TNFRSF 11B、ESRP 1、CSE 1 L和MMP 9具有良好的相关性。使用独立队列（n = 384）的进一步验证证实，只有8 q24内的MYC和TNFRSF 11B与生存相关。MYC和TNFRSF 11B均升高的患者生存率低于未升高的患者，尤其是非贲门癌患者。我们的研究结果显示，位于8 q24的MYC和TNFRSF 11B基因拷贝数的增加与胃癌的生存率相关，尤其是非贲门癌。
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.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).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.Our results revealed that copy number gains in MYC and TNFRSF11B located at 8q24 are associated with survival in GC, particularly noncardia GC.