FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer.
FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer.
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发表时间：
2013
影响因子：
1.4
通讯作者：
Masanori Kawakami;S. Morita;M. Sunohara;Y. Amano;Rie Ishikawa;Kousuke Watanabe;Emi Hamano;Nobuya Ohishi;J. Nakajima;Y. Yatomi;T. Nagase;M. Fukayama;D. Takai
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作者：
Masanori Kawakami;S. Morita;M. Sunohara;Y. Amano;Rie Ishikawa;Kousuke Watanabe;Emi Hamano;Nobuya Ohishi;J. Nakajima;Y. Yatomi;T. Nagase;M. Fukayama;D. Takai
在这里，我们发现，fer-tyrosine kinase（FER），一种非受体酪氨酸激酶的过度表达，预示着不良的术后结果，并可能参与非小细胞肺癌（NSCLC）的癌细胞存活。使用计算机分析和定量RT-PCR进行的系统筛选显示，FER在约10%的NSCLC患者中过表达。组织芯片免疫组化（IHC）评价FER表达与定量RT-PCR检测mRNA水平一致。在对135例接受潜在根治性切除术的NSCLC患者的分析中，我们发现使用IHC检测到的FER过表达与临床病理特征（如年龄、性别、吸烟史、组织学类型、疾病分期、T因子、N因子、辅助化疗史或EGFR突变）无关，但与术后生存期差相关。多变量考克斯回归分析显示，这种预后影响是独立的其他临床病理特征。在体外对FER的功能分析中，发现FER具有转化活性，提示其具有致癌功能。我们还发现，人肺癌NCI-H661细胞，表现出FER异常表达，导致凋亡的FER敲低使用RNA干扰。FER的过度表达可能作为一个预后的生物标志物，并参与癌细胞的生存在非小细胞肺癌。
Here, we show that overexpression of fer tyrosine kinase (FER), a non-receptor tyrosine kinase, predicts poor postoperative outcome and might be involved in cancer-cell survival in non-small cell lung cancer (NSCLC). Systematic screening using in silico analyses and quantitative RT-PCR revealed that FER was overexpressed in about 10% of NSCLC patients. Evaluation of FER expression using immunohistochemistry (IHC) on tissue microarrays was consistent with the mRNA level detected using quantitative RT-PCR. In analyses of 135 NSCLC patients who had undergone potential curative resection, we found that FER overexpression detected using IHC had no association with clinicopathological features such as age, sex, smoking history, histological type, disease stage, T factor, N factor, adjuvant chemotherapy history, or EGFR mutation, but was correlated with poor postoperative survival periods. A multivariate Cox regression analysis showed that this prognostic impact was independent of other clinicopathological features. In functional analyses of FER in vitro, FER exhibited a transforming activity, suggesting that it possesses oncogenic functions. We also found that human lung cancer NCI-H661 cells, which exhibited FER-outlier expression, were led to apoptosis by the knockdown of FER using RNA interference. FER overexpression might serve as a prognostic biomarker and be involved in cancer-cell survival in NSCLC.