Department of Electronic and Information Engineering, Perugia University, Italy.
Biotechnol Adv. 2012 Jan-Feb;30(1):142-53. doi: 10.1016/j.biotechadv.2011.05.010. Epub 2011 May 18.
In this paper we propose a Systems Biology approach to understand the molecular biology of the Epidermal Growth Factor Receptor (EGFR, also known as ErbB1/HER1) and type 1 Insulin-like Growth Factor (IGF1R) pathways in non-small cell lung cancer (NSCLC). This approach, combined with Translational Oncology methodologies, is used to address the experimental evidence of a close relationship among EGFR and IGF1R protein expression, by immunohistochemistry (IHC) and gene amplification, by in situ hybridization (FISH) and the corresponding ability to develop a more aggressive behavior. We develop a detailed in silico model, based on ordinary differential equations, of the pathways and study the dynamic implications of receptor alterations on the time behavior of the MAPK cascade down to ERK, which in turn governs proliferation and cell migration. In addition, an extensive sensitivity analysis of the proposed model is carried out and a simplified model is proposed which allows us to infer a similar relationship among EGFR and IGF1R activities and disease outcome.
在本文中，我们提出了一种系统生物学方法来理解非小细胞肺癌（NSCLC）中表皮生长因子受体（EGFR，也称为 ErbB1/HER1）和 1 型胰岛素样生长因子（IGF1R）途径的分子生物学。这种方法结合转化肿瘤学方法，通过免疫组织化学（IHC）和基因扩增，通过原位杂交（FISH）来解决 EGFR 和 IGF1R 蛋白表达之间的密切关系的实验证据，以及相应的发展更具侵略性行为的能力。我们基于常微分方程开发了一个详细的通路计算模型，并研究了受体改变对 MAPK 级联向下到 ERK 的时间行为的动态影响，ERK 反过来又控制增殖和细胞迁移。此外，对所提出的模型进行了广泛的敏感性分析，并提出了一个简化的模型，该模型允许我们推断出 EGFR 和 IGF1R 活性与疾病结果之间的类似关系。
