Aberrant expression of proteins involved in signal transduction and DNA repair pathways in lung cancer and their association with clinical parameters.
Aberrant expression of proteins involved in signal transduction and DNA repair pathways in lung cancer and their association with clinical parameters.
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肺癌信号转导和 DNA 修复途径相关蛋白的异常表达及其与临床参数的关系
DOI：
10.1371/journal.pone.0031087
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fang B
中科院分区：
文献类型：
--
作者：
He Y;Zhou Z;Hofstetter WL;Zhou Y;Hu W;Guo C;Wang L;Guo W;Pataer A;Correa AM;Lu Y;Wang J;Diao L;Byers LA;Wistuba II;Roth JA;Swisher SG;Heymach JV;Fang B
由于细胞信号传导和细胞代谢途径是通过蛋白质执行的，因此原发性肿瘤中的蛋白质特征对于识别信号网络中的关键节点非常有用，这些节点的改变与恶性肿瘤和/或临床结果相关。本研究旨在确定原发性肺癌组织中的蛋白特征。采用反相蛋白阵列（RPPA）分析了101例肺癌患者正常和肿瘤样本中126个蛋白和/或蛋白磷酸化位点。结果显示，18个分子在正常组织与肿瘤组织之间差异显著（p<0.05），差异不低于30%。这些分子大多在细胞增殖、DNA修复、信号转导和脂质代谢中起作用，或作为细胞表面/基质蛋白起作用。我们还通过Western blot和/或免疫组织化学分析验证了其中一些分子的RPPA结果。统计分析表明，不吸烟者的肿瘤中Ku80水平明显高于吸烟者。Cyclin B1水平在低分化肿瘤中显著过表达，Cox2水平在神经内分泌肿瘤中显著过表达。高水平的Stat5与接受手术治疗的患者有利的生存结果相关。结论/意义我们的研究结果揭示了肺癌组织中参与DNA损伤/修复、信号转导、脂质代谢和细胞增殖的一些分子明显异常，Stat5可能是肺癌预后的分子标志物。
Background Because cell signaling and cell metabolic pathways are executed through proteins, protein signatures in primary tumors are useful for identifying key nodes in signaling networks whose alteration is associated with malignancy and/or clinical outcomes. This study aimed to determine protein signatures in primary lung cancer tissues. Methodology/ Principal Findings We analyzed 126 proteins and/or protein phosphorylation sites in case-matched normal and tumor samples from 101 lung cancer patients with reverse-phase protein array (RPPA) assay. The results showed that 18 molecules were significantly different (p<0.05) by at least 30% between normal and tumor tissues. Most of those molecules play roles in cell proliferation, DNA repair, signal transduction and lipid metabolism, or function as cell surface/matrix proteins. We also validated RPPA results by Western blot and/or immunohistochemical analyses for some of those molecules. Statistical analyses showed that Ku80 levels were significantly higher in tumors of nonsmokers than in those of smokers. Cyclin B1 levels were significantly overexpressed in poorly differentiated tumors while Cox2 levels were significantly overexpressed in neuroendocrinal tumors. A high level of Stat5 is associated with favorable survival outcome for patients treated with surgery. Conclusions/ Significance Our results revealed that some molecules involved in DNA damage/repair, signal transductions, lipid metabolism, and cell proliferation were drastically aberrant in lung cancer tissues, and Stat5 may serve a molecular marker for prognosis of lung cancers.
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DOI：
10.1165/ajrcmb.26.5.4689
发表时间：
2002-05-01
影响因子：
6.4
作者：
Greenberg, AK;Basu, S;Lee, TC
通讯作者：
Lee, TC
影响因子：
5.3
作者：
Sanchez-Ceja, S. G.;Reyes-Maldonado, E.;Gutierrez-Castellanos, S.
通讯作者：
Gutierrez-Castellanos, S.
影响因子：
11.2
作者：
Fan, Tao;Li, Ruiyun;Jiang, Feng
通讯作者：
Jiang, Feng
影响因子：
56.9
作者：
Matsuoka, Shuhei;Ballif, Bryan A.;Elledge, Stephen J.
通讯作者：
Elledge, Stephen J.
影响因子：
56.9
作者：
Hirao, A;Kong, YY;Mak, TW
通讯作者：
Mak, TW