Gene expression profiles in lung cancer using cDNA rrays

吸烟是导致肺癌的主要原因。然而，只有一小部分吸烟者会患上肺癌。此外，越来越多从不吸烟的患者也会患上肺癌。对于那些从不吸烟的人来说，肺癌的原因是未知的。为了解决这个问题，我们与DCEG的Neil Caporaso博士及其同事合作，使用来自当前，过去和从不吸烟的患者的配对肺癌和正常样本检查基因表达谱。共使用了30名患者，每个吸烟状态组10例，并通过Affytron U133基因芯片处理样本进行分析。预处理后共分析了52份样本，其中包括7份来自从不吸烟者的肿瘤和7份正常肺组织。所有样本的非监督聚类分析显示，来自从不吸烟患者的7个肿瘤中有5个聚集在一起，而来自当前和过去吸烟者的肿瘤基本上无法区分。迄今为止，我们的结果为两个重要的见解提供了强有力的证据：1）尽管在临床上是可区分的，但来自非吸烟患者的大多数肺癌很可能是通过与吸烟患者不同的分子机制发展的。2)过去吸烟者的肺癌在分子上与目前吸烟者的肺癌相似，并且很可能是由于吸烟造成的损害而发生的。

Cigarette smoking is the leading cause of lung cancer. However, only a small portion of the patients who are smokers ever develop lung cancer. Furthermore, more and more patients who have never smoked also develop lung cancer. The cause of lung cancer for those who have never smoked is unknown. To address this question, we collaborated with Dr. Neil Caporaso and his colleagues at DCEG to examine gene expression profiles using paired lung cancer and normal samples from patients who are current, past, and never smokers. A total of 30 patients with 10 cases from each smoking status group were used and the samples were processed for analysis by the Affymetrix U133 GeneChips. A total 52 samples were analyzable after preprocessing which included 7 tumor and 7 normal lung tissues from never smokers among others. Non-supervised clustering analysis of all samples revealed that 5 of 7 tumors from never-smoking patients grouped together while tumors from current and past smokers were essentially indistinguishable. Our result to date provided strong evidence for two important insights: 1) although clinically distinguishable, a majority of lung cancers from non-smoking patients most likely developed via a different molecular mechanism from those that developed from patients who had smoked. 2) Lung tumors from past smokers are molecularly similar to those of the current smokers and most likely have occurred as a result of the damages caused by smoking.