Seoul National University Hospital develops effective liver cancer surveillance test

A collaborative research team in Korea discovered a liver cancer-specific biomarker and designed a simple blood test-based liver cancer monitoring method to measure the biomarker, thereby presenting a possibility of more convenient and effective diagnosis of liver cancer regardless of race, along with the presence and stage of liver disease.

The research team, led by professors Yoo Soo-Jong and Cho Eun-Joo of the Department of Gastroenterology at Seoul National University Hospital, and Professor Kim Yeong-Jun of the Biochemistry Lab of Yonsei University designed a test method to quantitatively analyze the methylation marker that is unique to liver cancer and presented the results of a study that measured the accuracy of the test based on 726 blood samples.

Liver cancer, the seventh most common cancer in Korea, has a very poor prognosis, with six out of 10 patients dying within five years of diagnosis. Accordingly, high-risk groups with risk factors such as cirrhosis and hepatitis viruses need to undergo regular monitoring and examinations.

However, it is difficult to accurately distinguish between the various liver diseases that high-risk individuals have and actual liver cancer with the existing surveillance tests. In addition, since liver cancer has a variety of causes and varies in its manifestation between different ethnic groups, it is difficult for existing surveillance methods to quickly discern the manifestation of liver cancer.

In order to find an effective surveillance test that could be applied to a wide range of liver cancer patients as well as high-risk groups, the research team focused on DNA methylation markers that are specific to liver cancer. As a result of cohort analysis of liver cancer patients comprising a wide range of ethnicities and stages of disease, the team found that the levels of methylation of two DNA markers (RNF135 and LDHB) were particularly high.

This research team designed a test method for quantification of the methylation levels of these markers by assigning scores. The team enhanced the convenience of the test by using the PCR technique, which can quickly diagnose the disease using only a small number of genes. In particular, the research team explained that the test method has the advantage of quantitatively analyzing changes in the quantity of liver cancer-related DNA in accordance with the stages of progression of liver cancer, which enables greater efficiency in monitoring the growth of liver cancer and selection of more effective treatments for each patient.

Furthermore, as a result of analysis using this test method on a total of 726 blood samples collected from 202 normal persons, 211 persons with the risk of liver cancer, 170 persons with early-stage liver cancer and 143 persons with late-stage liver cancer, the team weas able to identify positive liver cancer with a sensitivity of 57%. This was higher than the sensitivity of a conventional blood test that measures alpha-fetoprotein concentration in the blood (45%). In addition, as a result of the analysis of methylation levels along with the alpha-fetoprotein levels in the blood test, the team was able to correctly diagnose positive liver cancer in seven out of 10 cases.

The research team emphasized that the DNA methylation marker-based liver cancer diagnosis method not only supplements the clinical accuracy of existing surveillance tests, but is also a useful technique that can be used universally to diagnose liver cancer, which displays a wide range of appearances according to the ethnicities of patients and stages of liver cancer.

Prof. Yoo Soo-Jong of Seoul National University Hospital explained its significance by saying that "This study is very meaningful since it lays the technical foundation for more convenient monitoring of liver cancer in high-risk groups."

Professor Kim Yeong-Jun of Yonsei University added that, "With follow-up research, we will be able to deduce an AI-based model for the level of risk of liver cancer manifestation that takes into account the patient's clinical data and minute changes in the quantity of methylation marker in the blood."

The results of this study, conducted with the support by the National Research Foundation of Korea, were published in the international academic journal BMC Molecular Cancer.