Multiple biomarker tissue arrays: A computational approach to identifying protein-protein interactions in the EGFR/ERK signalling pathway.

Q2 Biochemistry, Genetics and Molecular Biology
V Medina Villaamil, G Aparicio Gallego, M Valladares-Ayerbes, I Santamarina Caínzos, L Miguel Antón Aparicio
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引用次数: 1

Abstract

Unlabelled:

Background: Many studies have demonstrated genetic and environmental factors that lead to renal cell carcinoma (RCC) and that occur during a protracted period of tumourigenesis. It appears suitable to identify and characterise potential molecular markers that appear during tumourigenesis and that might provide rapid and effective possibilities for the early detection of RCC. EGFR activation induces cell cycle progression, inhibition of apoptosis and angiogenesis, promotion of invasion/metastasis, and other tumour promoting activities. Over-expression of EGFR is thought to play an important role in tumour initiation and progression of RCC because up-regulation of EGFR has been associated with high grade cancers and a worse prognosis.

Methods: Characterisation of the protein profile interacting with EGFR was performed using the following: an immunohistochemical (IHC) study of EGFR, a comprehensive computational study of EGFR protein-protein interactions, an analysis correlating the expression levels of EGFR with other significant markers in the tumourigenicity of RCC, and finally, an analysis of the utility of EGFR for prognosis in a cohort of patients with renal cell carcinoma.

Results: The cases that showed a higher level of this protein fell within the clear cell histological subtype (p = 0.001). The EGFR significance statistic was found with respect to a worse prognosis. In vivo significant correlations were found with PDGFR-β, Flk-1, Hif1-α, proteins related to differentiation (such as DLL3 and DLL4 ligands), and certain metabolic proteins such as Glut5. In silico significant associations gave us a panel of 32 EGFR-interacting proteins (EIP) using the APID and STRING databases.

Conclusions: This work summarises the multifaceted role of EGFR in the pathology of RCC, and it identifies EIPs that could help to provide mechanistic explanations for the different behaviours observed in tumours.

Abstract Image

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多种生物标志物组织阵列:一种识别EGFR/ERK信号通路中蛋白-蛋白相互作用的计算方法。
背景:许多研究表明遗传和环境因素可导致肾细胞癌(RCC),并发生在肿瘤发生的长期过程中。它似乎适合于识别和表征肿瘤发生过程中出现的潜在分子标记,并可能为早期检测RCC提供快速有效的可能性。EGFR激活可诱导细胞周期进程,抑制细胞凋亡和血管生成,促进侵袭/转移和其他肿瘤促进活动。EGFR的过度表达被认为在RCC的肿瘤发生和进展中起重要作用,因为EGFR的上调与高级别癌症和较差的预后有关。方法:通过以下方法对与EGFR相互作用的蛋白谱进行表征:EGFR的免疫组织化学(IHC)研究,EGFR蛋白-蛋白相互作用的综合计算研究,分析EGFR表达水平与RCC致瘤性中其他重要标志物的相关性,最后分析EGFR对肾癌患者预后的作用。结果:该蛋白水平较高的病例属于透明细胞组织学亚型(p = 0.001)。EGFR在预后较差的患者中具有统计学意义。体内与PDGFR-β、Flk-1、Hif1-α、分化相关蛋白(如DLL3和DLL4配体)以及某些代谢蛋白(如Glut5)存在显著相关性。通过使用APID和STRING数据库,我们获得了32个egfr相互作用蛋白(EIP)。结论:这项工作总结了EGFR在RCC病理中的多方面作用,并确定了可能有助于为肿瘤中观察到的不同行为提供机制解释的eip。
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来源期刊
Journal of Molecular Signaling
Journal of Molecular Signaling Biochemistry, Genetics and Molecular Biology-Biochemistry
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期刊介绍: Journal of Molecular Signaling is an open access, peer-reviewed online journal that encompasses all aspects of molecular signaling. Molecular signaling is an exponentially growing field that encompasses different molecular aspects of cell signaling underlying normal and pathological conditions. Specifically, the research area of the journal is on the normal or aberrant molecular mechanisms involving receptors, G-proteins, kinases, phosphatases, and transcription factors in regulating cell proliferation, differentiation, apoptosis, and oncogenesis in mammalian cells. This area also covers the genetic and epigenetic changes that modulate the signaling properties of cells and the resultant physiological conditions.
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