HMN 2026: How Simple blood test may help identify colorectal cancer patients at higher risk for recurrence and death

A new study led by researchers at Moffitt Cancer Center found that blood-based DNA markers known as protein epiScores can help predict which colorectal cancer patients face a higher risk of cancer recurrence or death. Results of the study were published in Clinical Epigenetics.

Researchers identified four protein epiScores that were strongly associated with worse outcomes, with patients showing higher levels experiencing a 60% to 70% greater risk of recurrence. One marker, LGALS3BP, was also linked to overall survival, with higher scores associated with an 80% increased risk of death during follow-up.

When added to standard clinical factors such as cancer stage and patient age, protein epiScores modestly but significantly improved the ability to predict outcomes. Prediction accuracy for recurrence increased from 64% to 70%, while accuracy for overall survival rose from 70% to 75%.

The findings suggest these blood-based epigenetic markers capture information about immune function, blood vessel growth and coagulation that is not reflected in traditional prognostic tools. While the approach requires validation in additional patient populations, the results demonstrate the potential of using a simple blood draw taken before treatment to refine risk assessment in colorectal cancer.

Jacob Kresovich, Ph.D., lead author and assistant member in the Cancer Epidemiology Program at Moffitt, answered questions about the research.

What is the biggest takeaway from this research?

We wanted to know whether a new blood-based test could better identify colorectal cancer patients at higher risk for recurrence or death. Doctors typically rely on tumor and patient characteristics, but those factors do not fully explain why patients with similar profiles can have very different outcomes. We tested whether protein epiScores could add useful information beyond standard clinical factors. Better prediction could help tailor follow-up care and treatment intensity while avoiding unnecessary interventions for lower-risk patients.

What are protein epiScores, and why use them instead of traditional blood protein tests?

Protein epiScores are based on DNA methylation patterns in blood cells. They act like a fingerprint of the immune cell’s state related to certain protein signals, rather than measuring protein levels directly. We used them because protein levels can fluctuate from day to day, while DNA methylation patterns tend to be more stable over time. These scores may also capture broader immune-related processes that could be more relevant to cancer progression.

Which findings stood out most for predicting patient outcomes?

Four protein epiScores were strongly linked to cancer recurrence: HCII, VEGFA, CCL17, and LGALS3BP. Patients with higher scores were about 60% to 70% more likely to experience recurrence. The LGALS3BP score was also strongly associated with overall survival, with higher levels linked to an 80% greater risk of death. These markers reflect different biological systems, including blood clotting, tumor blood vessel growth, and immune regulation, suggesting that multiple pathways influence cancer outcomes.

How did protein epiScores improve prediction beyond standard clinical factors like stage and age?

Using only traditional clinical factors, our model predicted recurrence with about 64% accuracy. Adding the four key protein epiScores increased accuracy to 70%. For overall survival, accuracy improved from 70% to 75% when the LGALS3BP score was added. We also saw improved risk classification, with more accurate prediction for 34% of patients for recurrence and 16% for mortality. Unfortunately, we were lacking information from circulating tumor DNA, so we will need to account for that in future studies, but even the small improvements shown here can have meaningful clinical impact.

What do these results suggest about future colorectal cancer care or research?

These findings suggest protein epiScores could eventually be incorporated into tools that help guide treatment and follow-up decisions. More broadly, the study shows that useful prognostic information can be obtained from a simple blood draw taken before treatment begins. Because these scores reflect relatively stable immune characteristics, they may help explain why some patients have poorer outcomes. However, the findings must be validated in other populations before clinical use.

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