Abstract
Background: Preoperative and postoperative evaluation of colorectal cancer (CRC) patients is crucial for subsequent treatment guidance. Our study aims to provide a timely and rapid assessment of the prognosis of CRC patients with deep learning according to non-invasive preoperative computed tomography (CT) and explore the underlying biological explanations. Methods: A total of 808 CRC patients with preoperative CT (development cohort: n = 426, validation cohort: n = 382) were enrolled in our study. We proposed a novel end-to-end Multi-Size Convolutional Neural Network (MSCNN) to predict the risk of CRC recurrence with CT images (CT signature). The prognostic performance of CT signature was evaluated by Kaplan-Meier curve. An integrated nomogram was constructed to improve the clinical utility of CT signature by combining with other clinicopathologic factors. Further visualization and correlation analysis for CT deep features with paired gene expression profiles were performed to reveal the molecular characteristics of CRC tumors learned by MSCNN in radiographic imaging. Results: The Kaplan-Meier analysis showed that CT signature was a significant prognostic factor for CRC disease-free survival (DFS) prediction [development cohort: hazard ratio (HR): 50.7, 95% CI: 28.4-90.6, p < 0.001; validation cohort: HR: 2.04, 95% CI: 1.44-2.89, p < 0.001]. Multivariable analysis confirmed the independence prognostic value of CT signature (development cohort: HR: 30.7, 95% CI: 19.8-69.3, p < 0.001; validation cohort: HR: 1.83, 95% CI: 1.19-2.83, p = 0.006). Dimension reduction and visualization of CT deep features demonstrated a high correlation with the prognosis of CRC patients. Functional pathway analysis further indicated that CRC patients with high CT signature presented down-regulation of several immunology pathways. Correlation analysis found that CT deep features were mainly associated with activation of metabolic and proliferative pathways. Conclusions: Our deep learning based preoperative CT signature can effectively predict prognosis of CRC patients. Integration analysis of multi-omic data revealed that some molecular characteristics of CRC tumor can be captured by deep learning in CT images.