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结肠癌进展的数据驱动数学模型。

Data Driven Mathematical Model of Colon Cancer Progression.

作者信息

Kirshtein Arkadz, Akbarinejad Shaya, Hao Wenrui, Le Trang, Su Sumeyye, Aronow Rachel A, Shahriyari Leili

机构信息

Department of Mathematics and Statistics, University of Massachusetts Amherst, Amherst, MA 01003-9305, USA.

Department of Mathematics, Pennsylvania State University, University Park, State College, PA 16802, USA.

出版信息

J Clin Med. 2020 Dec 5;9(12):3947. doi: 10.3390/jcm9123947.

Abstract

Every colon cancer has its own unique characteristics, and therefore may respond differently to identical treatments. Here, we develop a data driven mathematical model for the interaction network of key components of immune microenvironment in colon cancer. We estimate the relative abundance of each immune cell from gene expression profiles of tumors, and group patients based on their immune patterns. Then we compare the tumor sensitivity and progression in each of these groups of patients, and observe differences in the patterns of tumor growth between the groups. For instance, in tumors with a smaller density of naive macrophages than activated macrophages, a higher activation rate of macrophages leads to an increase in cancer cell density, demonstrating a negative effect of macrophages. Other tumors however, exhibit an opposite trend, showing a positive effect of macrophages in controlling tumor size. Although the results indicate that for all patients the size of the tumor is sensitive to the parameters related to macrophages, such as their activation and death rate, this research demonstrates that no single biomarker could predict the dynamics of tumors.

摘要

每一例结肠癌都有其独特的特征,因此对相同治疗的反应可能不同。在此,我们针对结肠癌免疫微环境关键成分的相互作用网络开发了一种数据驱动的数学模型。我们从肿瘤的基因表达谱估计每种免疫细胞的相对丰度,并根据患者的免疫模式对其进行分组。然后我们比较这些患者组中每一组的肿瘤敏感性和进展情况,并观察各组之间肿瘤生长模式的差异。例如,在幼稚巨噬细胞密度低于活化巨噬细胞的肿瘤中,巨噬细胞的较高活化率会导致癌细胞密度增加,表明巨噬细胞具有负面影响。然而,其他肿瘤呈现相反的趋势,显示巨噬细胞在控制肿瘤大小方面具有积极作用。尽管结果表明,对于所有患者而言,肿瘤大小对与巨噬细胞相关的参数敏感,如它们的活化率和死亡率,但这项研究表明,没有单一生物标志物能够预测肿瘤的动态变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f497/7762015/4f49bd47ec07/jcm-09-03947-g0A1.jpg

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