New Blood Test Could Help Predict Which Colorectal Cancer Patients Are at Higher Risk
Patients with colorectal cancer may soon have a better way to understand risk after diagnosis, thanks to a new blood-based research approach developed by researchers at Moffitt Cancer Center. Results of their study were published in Clinical Epigenetics. The approach looks at patterns in immune cell DNA collected from a routine blood draw and may help identify which patients are more likely to see their cancer return or have poorer survival.
— Moffitt Cancer Center (@MoffittNews) February 9, 2026
Jacob Kresovich, PhD
“We wanted to know whether a new blood-based test could better identify colorectal cancer patients at higher risk for recurrence or death,” said Jacob Kresovich, PhD, assistant member in the Cancer Epidemiology Department at Moffitt and the study’s senior author. “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.”
The study focuses on markers known as Protein EpiScores, which are based on chemical modifications to the DNA of blood cells. Patterns of these modifications are linked to biological processes such as immune function, blood vessel growth and blood clotting. In the study, researchers found that patients with higher levels of four specific Protein EpiScores had a 60% to 70% higher risk of colorectal cancer recurrence.
“What was striking is that these markers reflect very different biological processes,” Kresovich said. “This suggests that multiple pathways could be influencing who does well and who does not.”
One marker was also strongly associated with overall survival, with higher levels linked to an 80% increased risk of death during follow-up.
‘Act Like a Fingerprint’
Protein EpiScores differ from traditional blood tests that measure protein levels directly.
“Protein EpiScores act like a fingerprint of the immune system’s state related to certain circulating proteins,” Kresovich said. “Directly measured protein levels can fluctuate from day to day, while DNA methylation signatures related to these proteins are more stable over time, giving us a longer-term snapshot of what may be happening in the body.”
Alicia Richards, PhD
When researchers added Protein EpiScores to standard clinical factors such as cancer stage and patient age, they saw modest but meaningful improvements in how accurately outcomes could be predicted. Prediction accuracy for cancer recurrence increased from 64% to 70%, while accuracy for overall survival rose from 70% to 75%.
“Even small improvements in prediction can have meaningful clinical impact,” Alicia Richards, PhD, a research scientist at Moffitt and the study’s lead author said. “Better prediction could help tailor follow-up care and treatment intensity while avoiding unnecessary interventions for lower-risk patients.”
What Does This Mean For Patients?
For patients and families facing colorectal cancer, uncertainty about what comes next can be one of the most difficult aspects of diagnosis and treatment. Even when tumors share similar characteristics, patient outcomes can vary widely. More precise prediction tools could help clinicians better match surveillance and treatment strategies to a patient’s true level of risk.
“These findings suggest Protein EpiScores could eventually be incorporated into tools that help guide treatment and follow-up decisions,” Kresovich said. “More broadly, the study shows that we can find useful prognostic information from a simple blood draw taken before treatment begins.”
Researchers caution that the findings represent an early proof of concept.
“Our results need to be validated in other populations before clinical use,” Kresovich said. “This is not a ready-to-use test, but it shows that this approach has real potential.”
Colorectal cancer remains one of the most common cancers in the United States. As research into blood-based diagnostics continues to advance, approaches that use Protein EpiScores may one day help provide patients and clinicians with clearer insight into risk and disease progression.
