Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma.
Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma.
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DOI：
10.1038/sj.bjc.6603614
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发表时间：
2007-03-12
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
盘状结构域受体（DDR）1和DDR2与许多人类癌症有关。我们试图确定人类肺癌中DDRs的表达水平，研究预后决定因素，并确定最近报道的这些受体酪氨酸激酶突变的患病率。采用实时定量PCR（qRT-PCR）分析了146例非小细胞肺癌（NSCLC）患者的肿瘤样本中DDR 1和DDR2的相对表达。另外23个匹配的肿瘤和正常组织进行了DDR 1和DDR2的差异表达测试，以及先前报道的体细胞突变。发现盘状结构域受体1在肿瘤与正常肺组织中显著上调2.15倍（P=0.0005），DDR2显著下调至同等程度（P=0.0001）。盘状结构域受体2的表达不能预测患者的生存率;然而，DDR 1的表达与总体（风险比（HR）0.43，95%CI =0.22-0.83，P=0.014）和无病生存率（HR=0.56，95%CI =0.33-0.94，P=0.029）显著相关。多变量分析显示，DDR 1是独立于肿瘤分化、分期、组织学和患者年龄的预后的独立有利预测因子。然而，与以前的工作相反，我们没有观察到DDR突变。我们的结论是，而改变表达的DDRs可能有助于恶性进展的非小细胞肺癌，这是不太可能的结果，在DDR 1和DDR2基因的突变，我们调查。
The discoidin domain receptors, (DDR)1 and DDR2, have been linked to numerous human cancers. We sought to determine expression levels of DDRs in human lung cancer, investigate prognostic determinates, and determine the prevalence of recently reported mutations in these receptor tyrosine kinases. Tumour samples from 146 non-small cell lung carcinoma (NSCLC) patients were analysed for relative expression of DDR1 and DDR2 using quantitative real-time PCR (qRT-PCR). An additional 23 matched tumour and normal tissues were tested for differential expression of DDR1 and DDR2, and previously reported somatic mutations. Discoidin domain receptor 1 was found to be significantly upregulated by 2.15-fold (P=0.0005) and DDR2 significantly downregulated to an equivalent extent (P=0.0001) in tumour vs normal lung tissue. Discoidin domain receptor 2 expression was not predictive for patient survival; however, DDR1 expression was significantly associated with overall (hazard ratio (HR) 0.43, 95% CI=0.22–0.83, P=0.014) and disease-free survival (HR=0.56, 95% CI=0.33–0.94, P=0.029). Multivariate analysis revealed DDR1 is an independent favourable predictor for prognosis independent of tumour differentiation, stage, histology, and patient age. However, contrary to previous work, we did not observe DDR mutations. We conclude that whereas altered expression of DDRs may contribute to malignant progression of NSCLC, it is unlikely that this results from mutations in the DDR1 and DDR2 genes that we investigated.
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影响因子：
11.2
作者：
Barsyte-Lovejoy, Dalia;Lau, Suzanne K.;Penn, Linda Z.
通讯作者：
Penn, Linda Z.
影响因子：
20.1
作者：
Hou, GP;Vogel, WF;Bendeck, MP
通讯作者：
Bendeck, MP
影响因子：
6
作者：
Matsuyama, W;Watanabe, M;Arimura, K
通讯作者：
Arimura, K
影响因子：
4.4
作者：
Matsuyama, W;Watanabe, M;Arimura, K
通讯作者：
Arimura, K
影响因子：
3.9
作者：
Ram, R;Lorente, G;Nagavarapu, U
通讯作者：
Nagavarapu, U