HIGHER tumour vascular features were associated with differing colorectal cancer mortality outcomes in a prospective cohort study of 837 patients with colorectal cancer. The findings indicated that some vascular characteristics were associated with lower colorectal cancer-specific mortality, while others were associated with higher mortality.
The prospective cohort incident-tumour biobank method (PCIBM) was used to analyse data from the Nurses’ Health Study and Health Professionals Follow-up Study. Among 4,476 incident colorectal cancer cases, resected tumour tissue specimens were collected. Multispectral immunofluorescence and machine learning were used to characterise tumour vasculature.
The analysis examined vascular markers including atypical chemokine receptor 1 (ACKR1), cluster of differentiation 34 (CD34), cluster of differentiation 36 (CD36), kinase insert domain receptor (KDR), laminin subunit β1 (LAMB1), mucosal addressin cell adhesion molecule 1 (MADCAM1) and keratin (KRT). Vessels were morphologically classified as micro, collapsed, patent or irregular.
Tumour vascular features demonstrated contrasting associations with colorectal cancer-specific mortality. Among the 837 patients with colorectal cancer, the median age at diagnosis was 69 years, and 466 patients (56%) were female. During a median follow-up of 11.8 years among censored cases, 628 all-cause deaths occurred, including 263 colorectal cancer-specific deaths.
Higher overall CD34+ vessel density was associated with lower colorectal cancer-specific mortality. Patients in the highest quartile had a hazard ratio (HR): 0.39; 95% CI: 0.25–0.60; p for trend<0.001, compared with the lowest quartile.
A higher proportion of micro CD34+ vessels was also associated with lower mortality, with an HR: 0.48; 95% CI: 0.31–0.74; p for trend=0.004 for the highest quartile.
Conversely, higher proportions of CD34+CD36+ and CD34+LAMB1+ vessels were associated with higher colorectal cancer-specific mortality. The highest category of CD34+CD36+ vessels had an HR: 1.58; 95% CI: 1.07–2.32; p for trend=0.004. For CD34+LAMB1+ vessels, the corresponding HR was 1.78; 95% CI: 1.22–2.61; p for trend<0.001.
The findings suggest that tumour vascular features may reflect biologically distinct characteristics of the colorectal cancer tumour microenvironment. The contrasting mortality associations observed across vascular markers indicate that tumour vasculature may have prognostic relevance beyond overall vessel density.
The authors concluded that tumour vascular features could serve as prognostic biomarkers and potential therapeutic targets in colorectal cancer. The study findings describe associations between vascular characteristics and colorectal cancer-specific mortality and do not establish causation.
Reference
Matsuda K et al. Tumor vascular features and colorectal cancer–specific mortality. JAMA Netw Open. 2026;9(9):e2634883.
Featured Image: Dr_Microbe on Adobe Stock
Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.
