Department of Predictive and Preventive Medicine, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy.
Int J Cancer. 2012 Sep 1;131(5):E643-8. doi: 10.1002/ijc.27426. Epub 2012 Feb 28.
Associations between clinical outcome of cancer patients and the gene expression signature in primary tumors at time of diagnosis have been reported. To test whether gene expression patterns in noninvolved lung tissue might correlate with clinical stage in lung adenocarcinoma (ADCA) patients, we compared the transcriptome of noninvolved lung samples from 60 ADCA smoker patients of clinical stage I versus 60 patients with stage>I. Quantitative PCR of 10 genes with the most significant differential expression confirmed the statistical association with clinical stage in eight genes, six of which were downregulated in high-stage patients. Five of these six genes were also downregulated in lung ADCA tissue as compared to noninvolved tissue. Studies in vitro indicated that four of the genes (SLC14A1, SMAD6, TMEM100 and TXNIP) inhibited colony formation of lung cancer cell lines transfected to overexpress the genes, suggesting their potential tumor-suppressor activity. Our findings suggest that individual variations in the transcriptional profile of noninvolved lung tissue may reflect the lung ADCA patient's predisposition to tumor aggressiveness.
已经有报道称，癌症患者的临床结果与诊断时原发性肿瘤的基因表达特征之间存在关联。为了测试非受累肺组织中的基因表达模式是否与肺腺癌（ADCA）患者的临床分期相关，我们比较了 60 例临床 I 期 ADCA 吸烟者的非受累肺样本和 60 例 I 期以上患者的转录组。10 个具有最显著差异表达的基因的定量 PCR 证实了 8 个基因与临床分期的统计学关联，其中 6 个在高分期患者中下调。这 6 个基因中有 5 个在肺 ADCA 组织中也下调。体外研究表明，其中 4 个基因（SLC14A1、SMAD6、TMEM100 和 TXNIP）抑制了过表达这些基因的肺癌细胞系的集落形成，表明它们具有潜在的肿瘤抑制活性。我们的研究结果表明，非受累肺组织转录谱的个体差异可能反映了肺 ADCA 患者对肿瘤侵袭性的易感性。
