Prognostic value of molecular events from negative surgical margin of non-small-cell lung cancer.
Prognostic value of molecular events from negative surgical margin of non-small-cell lung cancer.
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DOI：
10.18632/oncotarget.10949
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发表时间：
2017-08-08
期刊：
影响因子：
--
通讯作者：
Zhang K
中科院分区：
文献类型：
--
作者：
Cao B;Feng L;Lu D;Liu Y;Liu Y;Guo S;Han N;Liu X;Mao Y;He J;Cheng S;Gao Y;Zhang K
手术切缘阴性(NSM)的分子状态可能与癌症患者的预后有关。在这项研究中，研究了非小细胞肺癌患者NSM中上皮间充质转化(EMT)分子事件与预后的相关性。用转化生长因子-β1诱导人永生化支气管上皮细胞系间充质转化，建立EMT模型。应用基因芯片技术对60例肺鳞状细胞癌(SCC)患者EMT诱导的细胞和NSM的基因表达进行了分析，并用定量RT-PCR方法进行了验证。两个独立的队列(肺鳞癌，n=50；非小细胞肺癌，n=54)被用来验证候选基因的预后价值。在体外EMT模型中，共鉴定了1490个基因。在NSM中，由33个必需基因组成的EMT样基因表达模式被优化，并与肿瘤进展显著相关。这33个基因在邻近NSCLC的正常呼吸道中也表现出位置依赖性的野生性癌变效应。在独立的肺鳞状细胞癌队列中，EMT样活动模式表明患者预后较差(n=50，对数等级p=0.009)。此外，在NSCLC队列中，具有EMT样活动模式的患者的预测生存时间较短(n=54，log-ranking p=0.02)。综上所述，NSMS中EMT样基因表达的存在，可能在NSCLC患者的肿瘤进展过程中起关键作用，并可能成为判断NSCLC患者预后的潜在生物标志物。
It is hypothesized that the molecular status in negative surgical margin (NSM) is associated with prognosis of cancer patients. In this study, the prognostic relevance of Epithelial-to-Mesenchymal Transition (EMT) molecular events in NSMs in patients with NSCLC was investigated. EMT model was developed, in which the mesenchymal transition of human immortalized bronchial epithelial cell line was induced by TGF-beta1. Gene expression of EMT-induced cells and NSMs from 60 lung squamous cell carcinoma (SCC) patients was profiled by microarray and validated by quantitative RT-PCR. Two independent cohorts (lung SCC, n = 50; NSCLC, n = 54) were employed to validate the prognostic value of candidate genes. A set of 1490 genes were identified in EMT model in vitro. An EMT-like gene-expression pattern by 33 essential genes was optimized in NSMs, and was significantly associated with tumor progression. The 33 genes also exhibited a site-dependent field cancerization effect in the normal-appearing airways adjacent to NSCLCs. In the independent lung SCC cohort, the EMT-like active pattern indicated poor outcome of patients (n = 50, log-rank p = 0.009). Furthermore, in the NSCLC cohort, patients with EMT-like active pattern had shorter predictive survival time (n = 54, log-rank p = 0.02). In conclusion, the existence of EMT-like gene expression in NSMs, may play critical role in tumor progression and be a potential biomarker for prognosis in patients with NSCLC.
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