Association of the Collagen Signature in the Tumor Microenvironment With Recurrence and Survival of Patients With T4N0M0 Colon Cancer

BACKGROUND: The current clinicopathological risk factors do not accurately predict disease recurrence in patients with T4N0M0 colon cancer. We hypothesized that the collagen signature combined with clinicopathological risk factors (new model) had a better prognostic value than clinicopathological risk factors alone (clinicopathological model). OBJECTIVE: This study aimed to establish a collagen signature in the tumor microenvironment and to validate its role in predicting the recurrence of T4N0M0 colon cancer. DESIGN: This was a retrospective study. SETTINGS: This study took place at a tertiary medical center. PATIENTS: Patients with T4N0M0 colon cancer who underwent surgery at our center between 2009 and 2015 (n = 416) were included. INTERVENTION: A total of 142 collagen features were analyzed in the tumor microenvironment in specimens of colon cancer by using second-harmonic generation imaging. A collagen signature was constructed using a least-absolute shrinkage and selection operator Cox regression model. MAIN OUTCOME MEASURES: The primary outcomes measured were disease-free survival and overall survival. RESULTS: The training and testing cohorts consisted of 291 and 125 randomly assigned samples, with recurrence rates of 19.9% and 22.4%. A 3-feature-based collagen signature predicted the recurrence risk at 1, 3, and 5 years, with the area under the receiver-operating characteristic curves of 0.808, 0.832, and 0.791 in the training cohort and 0.836, 0.807, and 0.794 in the testing cohort. Multivariate analysis revealed that the collagen signature could independently predict the disease-free survival (HR = 7.17, p < 0.001) and overall survival rates (HR = 5.03, p < 0.001). The new model had a better prognostic value than the clinicopathological model, which included 4 clinicopathological risk factors: obstruction or perforation, lymphovascular invasion, tumor budding, and no chemotherapy. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The collagen signature in the tumor microenvironment may be a new prognostic marker that can effectively predict the recurrence and survival of patients with T4N0M0 colon cancer. See Video Abstract at http://links.lww.com/DCR/B503.

Automated summary

This study established a collagen signature in the tumor microenvironment to effectively predict recurrence and survival in patients with T4N0M0 colon cancer. The new model combining collagen signature with clinicopathological risk factors showed better prognostic value than the clinicopathological model alone.