Identification of metastasis-associated receptor tyrosine kinases in non-small cell lung cancer
Identification of metastasis-associated receptor tyrosine kinases in non-small cell lung cancer
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DOI：
10.1158/0008-5472.can-04-3388
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发表时间：
2005-03-01
期刊：
影响因子：
11.2
通讯作者：
Serve, H
中科院分区：
文献类型：
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作者：
Müller-Tidow, C;Diederichs, S;Serve, H
肿瘤切除后远处转移的发展是早期非小细胞肺癌（NSCLC）死亡的主要原因。受体酪氨酸激酶（RTK）参与肿瘤的发生，但只有少数RTK在NSCLC中进行了系统研究。在此，我们提供了70例早期（I-IIIA）NSCLC患者原发肿瘤中所有RTK（n = 56）的定量实时逆转录-PCR表达数据。总体而言，至少25%的患者表达了33种RTK。几种RTK在最终转移的肿瘤中显著表达更高。对于胰岛素受体、神经营养酪氨酸受体激酶1、表皮生长因子受体、ERBB 2、ERBB 3、血小板源性生长因子受体β、成纤维细胞生长因子受体1或白细胞酪氨酸激酶高表达水平的肿瘤，I/II期疾病发生转移的危险风险至少增加3倍。EPHB 6或DKFZ 1的表达使相对风险降低3倍。表皮生长因子受体家族的三个成员与转移的高风险相关，强调了我们数据的有效性。ERBB 3高表达与生存率降低显著相关。总之，我们的全基因组RTK表达图谱揭示了以前未知的几种RTK作为早期NSCLC预后和转移预测的潜在标志物的价值。所确定的RTK代表有前途的新的候选人进行进一步的功能分析。
Development of distant metastasis after tumor resection is the leading cause of death in early-stage non-small cell lung cancer (NSCLC). Receptor tyrosine kinases (RTK) are involved in tumorigenesis but only few RTKs have been systematically studied in NSCLC. Here, we provide quantitative real-time reverse transcription-PCR expression data of all RTKs (n = 56) in primary tumors of 70 patients with early-stage (I-IIIA) NSCLC. Overall, 33 RTKs were expressed in at least 25% of the patients. Several RTKs were significantly expressed higher in tumors that ultimately metastasized. The hazard risk for metastasis development in stage I/II disease was increased at least 3-fold for tumors with high expression levels of insulin receptor, neurotrophic tyrosine receptor kinase 1, epidermal growth factor receptor, ERBB2, ERBB3, platelet-derived growth factor receptor beta, fibroblast growth factor receptor 1, or leukocyte tyrosine kinase. Relative risks were reduced 3-fold by expression of EPHB6 or DKFZ1. Three members of the epidermal growth factor receptor family were associated with a high risk of metastasis, emphasizing the validity of our data. High ERBB3 expression was significantly associated with decreased survival. Taken together, our genome-wide RTK expression map uncovered the previously unknown value of several RTKs as potential markers for prognosis and metastasis prediction in early-stage NSCLC. The identified RTKs represent promising novel candidates for further functional analyses.