Data driven mathematical model of colon cancer progression

• Published in: bioRxiv
• Main Authors: Kirshtein, Arkadz, Shaya Akbarinejad, Hao, Wenrui, Le, Trang, Aronow, Rachel A, Shahriyari, Leili
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 04.11.2020
• Subjects: Adenocarcinoma; Advanced glycosylation end products; CCL20 protein; Cell activation; Cell density; Chemokines; Colitis; Colon cancer; Colorectal cancer; Dendritic cells; FasL protein; Gene expression; Genomes; Glycosylation; HMGB1 protein; Interferon; Ligands; Macrophages; Mathematical models; Microenvironments; Natural killer cells; NF-κB protein; Thymic stromal lymphopoietin; Thymus; Transcription; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumors
• DOI: 10.1101/2020.11.02.365668

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. Competing Interest Statement The authors have declared no competing interest. Footnotes * https://github.com/ShahriyariLab/Data-driven-mathematical-model-for-colon-cancer * https://github.com/ShahriyariLab/TumorDecon * Abbreviations CAC colitis-associated cancer CCL20 chemokine (C-C motif) ligand 20 COAD colon adenocarcinoma DAMP damage-associated molecular pattern DCs dendritic cells FasL fas ligand GEP gene expression profiles HMGB1 high mobility group box 1 IFN interferon IL interleukin NF-κB nuclear factor kappa B NK cells natural killer cells ODE ordinary differential equation RAGE receptor for advanced glycation endproducts RNA-seq ribonucleic acid sequencing STAT signal transducer and activator of transcription TAM tumor associated macrophage TCGA the cancer genome atlas TGF transforming growth factor TNF tumor necrosis factor TSLP thymic stromal lymphopoietin