Just a small sample of blood may be enough to help doctors catch liver cancer early, according to a new study published in the journal Gut.
A blood test analyzing compounds in DNA was able to identify liver cancer in patients without mistakenly flagging those merely at risk, according to Wei Zhang, PhD, associate professor of Preventive Medicine in the Division of Cancer Epidemiology and Prevention and a co-author of the study.
“This new, non-invasive blood test opens up new opportunities for clinical management of liver cancer, such as targeted screening in high-risk individuals, patient monitoring or screening in the general population,” said Zhang, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Biopsy is the normal gold standard for diagnosing liver cancer, but it is comparatively expensive, difficult and time-consuming. Currently available blood-based tests, however, perform poorly in detecting early-stage cancer, which is a particular problem in liver cancer: Treatment is drastically more difficult as this type of the cancer progresses.
For example, in a patient whose liver cancer has already spread to a distant part of the body, the five-year survival rate is only two percent — compared to a survival rate of 30 percent for patients whose cancer is diagnosed early, according to Zhang.
“After years of efforts to improve clinical outcomes, the five-year survival rates for liver cancer patients remain dismal,” Zhang said.
Developing early-stage detection strategies was a priority, so Zhang and his collaborators turned to 5-hydroxymethylcytosine (5hmC), a class of biochemical features in the human genome that mark active gene expression and are contained in fragments of DNA that float freely throughout the bloodstream.
Previous studies had observed a reduction in 5hmC in a wider variety of cancer genomes, so the investigators have focused on testing low levels of 5hmC as a potential cancer biomarker.
Working with Chuan He, PhD, the John T. Wilson Distinguished Service Professor at the University of Chicago, the investigators developed a “liquid biopsy” that could detect low 5hmC in less than five milliliters of blood.
The current study tested this biopsy in more than 2,500 individuals, including more than 1,200 liver cancer patients, finding the blood test vastly outperformed current blood tests by detecting about 88 percent of tumors. Further, the new test was able to identify early stage tumors without notable numbers of false positives from high-risk patients, such as those with a history of chronic hepatitis B virus infection (CHB) or liver cirrhosis, which confounded the current blood tests.
“Given the non-invasiveness — it’s just a blood draw — this new test has the potential to be routinely used in clinical surveillance for disease recurrence, such as monitoring patients after surgery or as a screening tool for the general population,” Zhang said. “This approach could have a huge clinical impact.”
Other Northwestern co-authors are Zhou Zhang, PhD, a postdoctoral fellow, who shared the first authorship, and Chang Zeng, a graduate student in the Driskill Graduate Program in Life Sciences, both members of Wei Zhang’s laboratory.
This study was supported by National Institutes of Health grants U01CA217078 and R01CA223662; Chinese State Key Project for Liver Cancer grant 2018ZX10732202-001; National Natural Science Foundation of China grants 81790633, 91729303, 81672860, 81572061, 81602513, 81472840, 81530077 and 81672825; The University of Chicago Ludwig Center and The Howard Hughes Medical Institute.
