Interrogating Patient-level Genomics and Mouse Phenomics towards Understanding Cytokines in Colorectal Cancer Metastasis

Background: Colorectal cancer is the second leading cancer-related death worldwide and a majority of patients die from metastasis. Chronic intestinal inflammation plays an important role in tumor progression of colorectal cancer. However, few study works on systematically predicting colorectal cancer metastasis using inflammatory cytokine genes. Results: We developed a supervised machine learning approach to predict colorectal cancer tumor progression using patient level genomic features. To better understand the role of cytokines, we integrated the metastatic-related genes from mouse phenotypic data. In addition, pathway analysis and network visualization were also applied to top significant genes ranked by feature weights of the final prediction model. The combined model of cytokines and mouse phenotypes achieved a predictive accuracy of 75.54%, higher than the model based on mouse phenotypes independently (70.42%, p-value<0.05). In additional, the combined model outperformed the model based on the existing metastatic-related epithelial-to-mesenchymal transition (EMT) genes (75.54% vs. 71.61%, p-value<0.05). We also observed that the most important cytokine gene features of the our model interact with the cancer driver genes and are highly associated with the colorectal cancer metastasis signaling pathway. Conclusion: We developed a combined model using both cytokine and mouse phenotype information to predict colorectal cancer metastasis. The results suggested that the inflammatory cytokines increase the power of predicting metastasis. We also systematically demonstrated the critical role of cytokines in progression of colorectal tumor.