Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer
Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer
复制标题
DOI：
10.1038/sj.bjc.6605734
复制
发表时间：
2010-07-13
影响因子：
8.8
通讯作者：
Miyazaki, M.
中科院分区：
文献类型：
--
作者：
Takano, S.;Sogawa, K.;Miyazaki, M.
背景：细胞内磷蛋白激活显着调节癌症进展。然而，血液中循环磷蛋白的重要性仍然未知。我们通过一种全面测量血清磷蛋白水平的新方法研究了胰腺癌（PaCa）中涉及的血清磷蛋白谱，并将该方法临床应用于PaCa的检测。方法：我们通过比较PaCa患者和良性对照（包括健康志愿者（HV）和胰腺炎）的血清，分析了包含癌细胞信号通路的血清磷蛋白。 结果：PaCa 患者和 HV 之间的层次聚类分析揭示了不同的通路特异性特征。特别是，与 HV 相比，PaCa 患者血清中细胞外信号调节激酶 (ERK) 信号通路的成分显着增加。对于早期 PaCa，p-ERK1/2 的阳性率（82%）优于 CA19-9（53%）。对于这些血清水平的组合，接受者-操作者特征曲线下面积显示出区分独立验证集中的两个群体以及另一个验证集中的癌症和非癌症群体的显着能力。 结论：血清细胞信号磷蛋白的综合测量对于PaCa的检测是有用的。进一步的研究将导致实施量身定制的分子靶向疗法。英国癌症杂志 (2010) 103, 223-231。 doi: 10.1038/sj.bjc.6605734 www.bjcancer.com 在线发布 2010 年 6 月 15 日 (C) 2010 英国癌症研究中心
BACKGROUND: Intracellular phosphoprotein activation significantly regulates cancer progression. However, the significance of circulating phosphoproteins in the blood remains unknown. We investigated the serum phosphoprotein profile involved in pancreatic cancer (PaCa) by a novel approach that comprehensively measured serum phosphoproteins levels, and clinically applied this method to the detection of PaCa.METHODS: We analysed the serum phosphoproteins that comprised cancer cellular signal pathways by comparing sera from PaCa patients and benign controls including healthy volunteers (HVs) and pancreatitis patients.RESULTS: Hierarchical clustering analysis between PaCa patients and HVs revealed differential pathway-specific profiles. In particular, the components of the extracellular signal-regulated kinase (ERK) signalling pathway were significantly increased in the sera of PaCa patients compared with HVs. The positive rate of p-ERK1/2 (82%) was found to be superior to that of CA19-9 (53%) for early stage PaCa. For the combination of these serum levels, the area under the receiver-operator characteristics curves was showing significant ability to distinguish between the two populations in independent validation set, and between cancer and non-cancer populations in another validation set.CONCLUSION: The comprehensive measurement of serum cell signal phosphoproteins is useful for the detection of PaCa. Further investigations will lead to the implementation of tailor-made molecular-targeted therapeutics. British Journal of Cancer (2010) 103, 223-231. doi: 10.1038/sj.bjc.6605734 www.bjcancer.com Published online 15 June 2010 (C) 2010 Cancer Research UK