Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue
Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue
复制标题
DOI：
10.1002/ijc.27426
复制
发表时间：
2012-09-01
影响因子：
6.4
通讯作者：
Dragani, Tommaso A.
中科院分区：
文献类型：
--
作者：
Frullanti, Elisa;Colombo, Francesca;Dragani, Tommaso A.
已经报道了癌症患者的临床结果与诊断时原发性肿瘤中的基因表达特征之间的关联。为了测试非受累肺组织中的基因表达模式是否可能与肺腺癌（ADCA）患者的临床分期相关，我们比较了来自60名临床I期ADCA吸烟者患者与60名>I期患者的非受累肺样本的转录组。定量PCR的10个基因的最显着的差异表达证实了统计学关联与临床分期的8个基因，其中6个在高阶段的患者下调。这六个基因中的五个也在肺ADCA组织中下调，与非受累组织相比。体外研究表明，其中4个基因（SLC14A1、SMAD6、TMEM100和TXNIP）可抑制转染过表达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，个体差异的转录谱的非参与肺组织可能反映了肺ADCA患者的易感性，肿瘤的侵略性。
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.