Laboratory Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
PLoS One. 2013 Apr 23;8(4):e62171. doi: 10.1371/journal.pone.0062171. Print 2013.
Metastasis is the most common cause of disease failure and mortality for non-small cell lung cancer after surgical resection. Twist has been recently identified as a putative oncogene and a key regulator of carcinoma metastasis. N-cadherin is associated with a more aggressive behavior of cell lines and tumors. The aim of this study was to evaluate the clinical relevance of Twist and N-cadherin expression in NSCLC, and the effects of Twist1 knockdown on lung cancer cells.
We examined the expressions of Twist and N-cadherin by immunohistochemistry in 120 cases of non-small cell lung cancer (including 68 cases with follow-up records). We also analyzed Twist1 and N-cadherin mRNA expression in 30 non-small cell lung cancer tissues using quantitative reverse transcription polymerase chain reaction. The functional roles of Twist1 in lung cancer cell lines were evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell apoptosis and invasion.
In lung cancer tissues, the overexpression rate of Twist was 38.3% in lung cancer tissues. Overexpression of N-cadherin was shown in 40.83% of primary tumors. Moreover, Twist1 mRNA expression levels correlated with N-cadherin mRNA levels. Furthermore, overexpression of Twist1 or N-cadherin in primary non-small cell lung cancers was associated with a shorter overall survival (P<0.01, P<0.01, respectively). Depleting Twist expression inhibited cell invasion and increased apoptosis in lung cancer cell lines.
The overexpression of Twist and N-cadherin could be considered as useful biomarkers for predicting the prognosis of NSCLC. Twist1 could inhibit apoptosis and promote the invasion of lung cancer cells, and depletion of Twist1 in lung cancer cells led to inhibition of N-cadherin expression.
非小细胞肺癌手术后转移是导致疾病失败和死亡的最常见原因。Twist 最近被确定为一种假定的癌基因和癌转移的关键调节因子。N-钙黏蛋白与细胞系和肿瘤更具侵袭性的行为有关。本研究旨在评估 Twist 和 N-钙黏蛋白在非小细胞肺癌中的临床相关性，以及 Twist1 敲低对肺癌细胞的影响。
我们通过免疫组织化学方法检测了 120 例非小细胞肺癌（包括 68 例有随访记录的病例）中 Twist 和 N-钙黏蛋白的表达情况。我们还使用定量逆转录聚合酶链反应分析了 30 例非小细胞肺癌组织中 Twist1 和 N-钙黏蛋白 mRNA 的表达情况。通过小干扰 RNA 介导的蛋白耗竭评估 Twist1 在肺癌细胞系中的功能作用，然后分析细胞凋亡和侵袭。
在肺癌组织中，Twist 的过表达率为 38.3%。在原发性肿瘤中，N-钙黏蛋白的过表达率为 40.83%。此外，Twist1 mRNA 表达水平与 N-钙黏蛋白 mRNA 水平相关。此外，原发性非小细胞肺癌中 Twist1 或 N-钙黏蛋白的过表达与总生存期缩短相关（P<0.01，P<0.01）。降低 Twist 表达抑制了肺癌细胞系的侵袭并增加了细胞凋亡。
Twist 和 N-钙黏蛋白的过表达可作为预测非小细胞肺癌预后的有用生物标志物。Twist1 可抑制细胞凋亡并促进肺癌细胞的侵袭，而肺癌细胞中 Twist1 的耗竭导致 N-钙黏蛋白表达的抑制。
