• National Natural Science Foundation of China

• Artificial intelligence
• Cancer
• Data integration
• Data science
• Decision support system
• Patient coaching
• Patient reported outcomes
• Predictive modeling
• Quality of life

Research interest in the role of inflammation in the progression and prognosis of colorectal cancer (CRC) is growing. In this study, we evaluated the expression and DNA methylation levels of inflammation-related genes in CRC tissues using the TCGA-COREAD dataset by integratively combining multi-omics features using machine learning. Statistical analysis was additionally performed to allow for interpretable, understandable, and clinically practical results. An integrative model combining expression, methylation, and clinical features had the highest performance. In multivariate analysis, the methylation levels of CEP250, RAB21, and TNPO3 were significantly associated with overall survival. Our study results implicate the importance of integrating expression and methylation information along with clinical information in the prediction of survival. CEP250, RAB21, and TNPO3 in the prediction model might have a crucial role in CRC prognosis and further improve our understanding of potential mechanisms linking inflammatory reactions and CRC progression.

Background inflammatory status indicators have been reported as prognostic biomarkers of colorectal cancer (CRC). However, since inflammatory interactions with the colon involve various modes of action, the biological mechanism linking inflammation and CRC prognosis has not been fully elucidated. We comprehensively evaluated the predictive roles of the expression and methylation levels of inflammation-related genes for CRC prognosis and their pathophysiological associations. Method. An integrative analysis of 247 patients with stage I-III CRC from The Cancer Genome Atlas was conducted. Lasso-penalized Cox proportional hazards regression (Lasso-Cox) and statistical Cox proportional hazard regression (CPH) were used for the analysis. Results. Models to predict overall survival were designed with respective combinations of clinical variables, including age, sex, stage, gene expression, and methylation. An integrative model combining expression, methylation, and clinical features performed better (median C-index = 0.756) than the model with clinical features alone (median C-index = 0.726). Based on multivariate CPH with features from the best model, the methylation levels of CEP250, RAB21, and TNPO3 were significantly associated with overall survival. They did not share any biological process in functional networks. The 5-year survival rate was 29.8% in the low methylation group of CEP250 and 79.1% in the high methylation group (p < 0.001). Conclusion. Our study results implicate the importance of integrating expression and methylation information along with clinical information in the prediction of survival. CEP250, RAB21, and TNPO3 in the prediction model might have a crucial role in CRC prognosis and further improve our understanding of potential mechanisms linking inflammatory reactions and CRC progression.

• TCGA
• colorectal cancer
• inflammatory genes
• multi-omics data

• R01 LM012535 NLM NIH HHS

Introducing deep learning approach to medical images has rendered a large amount of un-decoded information into usage in clinical research. But mostly, it has been focusing on the performance of the prediction modeling for disease-related entity, but not on the clinical implication of the feature itself. Here we analyzed liver imaging features of abdominal CT images collected from 2019 patients with stage I – III colorectal cancer (CRC) using convolutional neural network (CNN) to elucidate its clinical implication in oncological perspectives.

CNN generated imaging features from the liver parenchyma. Dimension reduction was done for the features by principal component analysis. We designed multiple prediction models for 5-year metachronous liver metastasis (5YLM) using combinations of clinical variables (age, sex, T stage, N stage) and top principal components (PCs), with logistic regression classification. The model using “1^st PC (PC1) + clinical information” had the highest performance (mean AUC = 0.747) to predict 5YLM, compared to the model with clinical features alone (mean AUC = 0.709). The PC1 was independently associated with 5YLM in multivariate analysis (beta = − 3.831, P < 0.001). For the 5-year mortality rate, PC1 did not contribute to an improvement to the model with clinical features alone. For the PC1, Kaplan-Meier plots showed a significant difference between PC1 low vs. high group. The 5YLM-free survival of low PC1 was 89.6% and the high PC1 was 95.9%. In addition, PC1 had a significant correlation with sex, body mass index, alcohol consumption, and fatty liver status.

The imaging features combined with clinical information improved the performance compared to the standardized prediction model using only clinical information. The liver imaging features generated by CNN may have the potential to predict liver metastasis. These results suggest that even though there were no liver metastasis during the primary colectomy, the features of liver imaging can impose characteristics that could be predictive for metachronous liver metastasis.

• Artificial intelligence
• Colorectal cancer
• Convolutional neural network
• Radiomics