Possible overtesting of liver cancer surveillance

The possibility of a simple and effective diagnosis of liver cancer regardless of race, stage, or liver disease has been proposed. Korean researchers have discovered liver cancer-specific biomarkers and designed a simple blood test-based liver cancer monitoring method to measure them.

Professors Soo-Jong Yoo and Eun-Joo Cho of the Department of Gastroenterology at Seoul National University Hospital and Professor Young-Jun Kim of Yonsei University's School of Biochemistry (researchers Sicho Kim and Da-Won Kim) designed a test method to quantitatively analyze methylation markers that only appear in liver cancer and measured the accuracy of the test based on 726 blood samples.

Liver cancer, the seventh most common cancer in Korea, has a poor prognosis, with six out of 10 patients dying within five years. Therefore, high-risk groups with risk factors such as cirrhosis and hepatitis viruses are regularly monitored.

However, existing surveillance tests cannot accurately distinguish between various liver diseases in high-risk individuals and actual liver cancer. In addition, liver cancer has many different causes and varies in appearance among different ethnic groups, making it difficult for existing surveillance methods to quickly identify the presence of liver cancer.

To find an effective surveillance method that can be applied to a wide range of liver cancer patients and those at high risk of liver cancer, the research team focused on DNA methylation markers that are specific to liver cancer.

*DNA methylation: a type of epigenetic phenomenon that regulates gene expression. Its occurrence can be altered by cancer cells, and some specific DNA methylation patterns have been used as biomarkers for cancer diagnosis.

In an analysis of a diverse cohort of liver cancer patients, two DNAs (RNF135 and LDHB) had uniquely high methylation levels. The team designed a test to score the methylation levels of these DNAs. They utilized the PCR technique, which can quickly diagnose disease using only a small amount of genes, for convenience.

In particular, the team's test is able to quantitatively analyze changes in the amount of liver cancer-associated DNA as the disease progresses. This makes it possible to monitor the growth of liver cancer and select the most effective treatment for each patient, according to the team.

Using this method, the researchers analyzed a total of 726 blood samples from 202 healthy individuals, 211 individuals at risk of liver cancer, 170 individuals with early-stage liver cancer, and 143 individuals with late-stage liver cancer, and found that the test was 57% sensitive in detecting positive liver cancer. This was higher than the sensitivity of a conventional blood test that measures alpha-fetoprotein concentration in the blood (45%).

Furthermore, when methylation levels and alpha-fetoprotein levels were analyzed together in the blood test, they were able to correctly diagnose positive liver cancer in seven out of 10 cases.

The researchers emphasized that DNA methylation marker-based liver cancer diagnosis not only complements the clinical accuracy of existing surveillance tests, but is also a useful technique that can be used universally to diagnose liver cancer, which has a diverse presentation across ethnicities and stages.

"This study is significant because it lays the technical foundation for easy monitoring of liver cancer in high-risk groups," said Dr. Yoo Soo-Jong, a professor of gastroenterology at Seoul National University Hospital.

"Through further research, we will derive an AI-based liver cancer risk model that takes into account the patient's clinical data and minute changes in the amount of methylation markers in the blood," said Yonsei professor Youngjun Kim.

The study, which was supported by the National Research Foundation of Korea, was published in the international journal BMC Molecular Cancer.