Collagen score in the tumor microenvironment predicts the prognosis of rectal cancer patients after neoadjuvant chemoradiotherapy

Abstract

Background and purpose: Little is known about the relationship between collagen and the prognosis of patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). This study aimed to quantitatively analyze collagen alterations, establish a collagen score (CS) in the tumor microenvironment, and evaluate and validate the relationship of the CS with prognosis in these patients.

Materials and methods: A total of 365 primary patients diagnosed with LARC after nCRT between 2011 and 2018 were retrospectively reviewed (training cohort: 210; independent validation cohort: 155). Multiple collagen features of two fields in the tumor microenvironment, the core of the tumor (CT) and the invasive margin (IM), were derived from multiphoton imaging, and the CS_IM-CT was generated using least absolute shrinkage and selection operator (LASSO) Cox regression analysis.

Results: The CS_IM-CT was created based on 3 features: collagen area, number of collagen fibers and a Gabor textural feature. In the training cohort, the CS_IM-CT predicted 3-year disease-free survival (DFS) with an area under the receiver operating characteristic curve (AUROC) of 0.765 (0.675-0.854) and an overall survival (OS) with AUROC of 0.822 (0.734-0.909). Additionally, the CS_IM-CT was significantly associated with DFS and OS in the two cohorts. A nomogram with the CS_IM-CT was developed and showed good prognostic value predicting a 3-year DFS with an AUROC of 0.826 (0.748-0.905) and an OS with AUROC of 0.882 (0.803-0.960).

Conclusions: The CS_IM-CT is an effective prognostic marker in patients with LARC after nCRT, and the nomogram with the CS_IM-CT can be used to accurately predict the individual prognosis of these patients.

Keywords: Collagen score; Neoadjuvant chemoradiotherapy; Nomogram; Prognosis; Rectal cancer; Tumor microenvironment.