Genome-Wide Analysis of Survival in Early-Stage Non-Small-Cell Lung Cancer
Genome-Wide Analysis of Survival in Early-Stage Non-Small-Cell Lung Cancer
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DOI：
10.1200/jco.2008.18.7906
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发表时间：
2009-06-01
影响因子：
45.3
通讯作者：
Christiani, David C.
中科院分区：
文献类型：
--
作者：
Huang, Yen-Tsung;Heist, Rebecca S.;Christiani, David C.
目的肺癌，其中85%是非小细胞肺癌（NSCLC），是美国癌症相关死亡的主要原因。我们使用全基因组肿瘤组织分析，以探讨是否单核苷酸多态性（SNPs）在肿瘤的预后因素在早期NSCLC.Patients和MethodsOne从马萨诸塞州总医院（MGH）的早期NSCLC患者被用作一个发现集和89收集的国家职业卫生研究所，挪威，NSCLC患者作为验证集。从具有至少70%肿瘤细胞的快速冷冻肺组织中提取DNA。使用高密度SNP芯片进行全基因组基因分型。在强度归一化后使用中值平滑来推断拷贝数。考克斯模型被用来筛选和验证显着的SNPs与总survival.Results3q，5p，和8q的染色体拷贝数增益在MGH和挪威队列观察。MGH队列中与总生存率相关的前50个SNP（P
PurposeLung cancer, of which 85% is non-small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC.Patients and MethodsOne hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival.ResultsCopy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P