Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
J Thorac Oncol. 2011 Nov;6(11):1833-40. doi: 10.1097/JTO.0b013e3182295917.
Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups.
Short-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters.
Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively.
Comprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.
非小细胞肺癌（NSCLC）的特征是存在多种未知临床影响的基因异常。在本研究中，我们旨在鉴定与 NSCLC 临床结果相关的基因拷贝数变化。为了最大限度地发现具有临床相关性的事件，我们采用了一种涉及两个预后极端患者群体的策略。
从具有可用新鲜冷冻肿瘤标本的临床特征明确的 NSCLC 患者队列中选择短期（<20 个月；n=53）和长期（>58 个月；n=47）幸存者。使用高分辨率单核苷酸多态性阵列技术分析样本，以评估基因拷贝数变化和基于阵列的基因表达谱。将分子数据与临床参数信息相结合。
遗传异常与肿瘤组织学密切相关。在腺癌（n=50）中，8q21-q24.3 染色体上的基因拷贝数增益（177 个基因）在长期幸存者中比在短期幸存者中更为常见。在鳞状细胞癌（n=28）中，14q23.1-24.3 染色体上的增益（133 个基因）与较短的生存时间相关，而相邻区域 14q31.1-32.33（110 个基因）的缺失与有利的结果相关。与拷贝数的增加和减少相一致，相应基因的信使 RNA 表达水平分别增加或减少。
全面的肿瘤分析允许整合基因组、组织学和临床数据。我们鉴定了与腺癌和鳞状细胞癌的预后相关的基因拷贝数增益和缺失，以及相应的信使 RNA 水平变化。
