The blood vessels coursing through colorectal tumors may reveal important clues about how a patient’s cancer will behave. New research suggests that both the number and type of vessels within a tumor are linked to the risk of dying from the disease, raising the possibility that tumor vasculature could become another tool for predicting prognosis.
The study, published in JAMA Network Open, found that patients whose tumors had a higher overall density of CD34-positive blood vessels had better outcomes. But greater proportions of two specific vessel types—those expressing CD34 along with CD36 or LAMB1—were associated with worse survival.
The findings suggest that tumor blood vessels are not all biologically equivalent. Identifying distinct vascular patterns could eventually add another layer of information to precision cancer profiling.
Researchers analyzed tumor samples from 837 patients with colorectal cancer (CRC) enrolled in the Nurses’ Health Study and Health Professionals Follow-up Study. Using multispectral immunofluorescence and computational image analysis, they characterized blood vessels based on their molecular markers as well as their size and shape.
During long-term follow-up, 263 patients died from CRC. Those whose tumors had the highest overall density of CD34-positive vessels had a 61% lower risk of CRC-specific death than patients with the lowest density, after accounting for other factors. A greater proportion of small CD34-positive vessels was also associated with better survival, including a 52% lower risk of CRC death among patients in the highest group.
That does not mean that simply having more blood vessels protects against cancer. Instead, vessel density may reflect other important features of the tumor microenvironment. Although blood vessels can fuel tumor growth by supplying oxygen and nutrients, they can also allow cancer-fighting immune cells to enter tumors and help anticancer drugs reach their targets.
When researchers looked more closely at the molecular characteristics of those vessels, a different pattern emerged.
Patients with the greatest proportion of CD34+CD36+ vessels had a 58% higher risk of CRC-specific death, while those with the greatest proportion of CD34+LAMB1+ vessels had a 78% higher risk.
CD36 and LAMB1 mark endothelial cell types involved in angiogenic sprouting, the process of forming new blood vessels. An abundance of these vessel types may signal more active angiogenesis and other tumor-promoting processes associated with worse outcomes.
The findings help sharpen the picture of the CRC tumor microenvironment: it may be the vascular profile—not simply whether a tumor has many or few blood vessels—that carries prognostic information.
That distinction could have implications for precision medicine. Vascular profiles might eventually complement existing molecular and pathological biomarkers to help identify patients with more aggressive disease. They could also highlight vascular pathways that warrant investigation as therapeutic targets.
The study was observational, so it cannot show that particular blood vessel features directly cause better or worse survival, and the findings will need validation in other patient populations.
Still, the results suggest that blood vessels could provide a previously underused source of information about CRC biology. Profiling the vessels within a tumor may ultimately help researchers better understand the cancer surrounding them—and potentially identify which patients face a poorer prognosis.
