CANCER DIGEST – June 25, 2022 – Researchers have identified a panel of four proteins that can be used to predict liver cancer risk in patients with nonalcoholic fatty liver disease (NAFLD) that might be used to track how well medications are working to reduce that risk. The results were published in the June 22, 2022 journal Science Translational Medicine.Nonalcoholic fatty liver disease (NAFLD) increases the risk of developing hepatocellular carcinoma (HCC), the most common form of liver cancer. An estimated one-quarter of US adults have NAFLD. Knowing which of their NAFLD patients were mostly likely to develop cancer would help doctors prescribe treatments that could reduce their patients’ risk.
The research led by Yujin Hoshida, M.D. and Naoto Fujiwara, M.D., PhD at the University of Texas Southwestern analyzed the blood from 409 NAFLD patients to find 133 genes that make proteins at higher or lower levels than average in the patients who developed liver cancer over a 15-year period. The patients were then stratified by high and low risk and 22.7 percent of the high-risk group were diagnosed with HCC, while no patients in the low-risk group developed HCC.
“This test was especially good at telling us who was in that low-risk group,” said Dr. Hoshida in a press release. He is the director of UTSW’s Liver Tumor Translational Research Program. “We can much more confidently say now that those patients don’t need to be followed very closely.”
The researchers then further defined the high-risk genes and developed a blood test for four proteins whose levels could be used for easier risk assessment. When NAFLD patients were sorted into low and high risk based on these four proteins they found that 37.6 percent of high-risk patients were diagnosed with HCC during the 15-year follow up period.
When the researchers analyzed the four proteins they discovered that all were involved in inflammatory processes, which points to the importance of inflammation to the development of HCC. They also found that the levels of these four proteins could be altered by certain therapies such as bariatric surgery, cholesterol drugs and immunotherapy.
“This means we could actually use these panels of molecules to track how well patients are doing over time or to inform potential effectiveness of medical interventions to reduce liver cancer risk,” said Dr. Hoshida. "For instance, the protein blood test, dubbed PLSec-NAFLD, is already being used to monitor the effectiveness of a cholesterol drug in reducing liver cancer risk in an ongoing clinical trial."
Sources: UTSW press release and Science Translational Medicine
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