A new blood test that detects changes in tumor DNA may allow doctors to diagnose liver cancer earlier and better monitor disease progression. Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults and over 40,000 people will be diagnosed in the US this year. The five year survival rate is 31% and if the cancer spreads to other regions, that rate drops to about 11%. This poor prognosis highlights the need for improved early detection measures. Currently, one of the first diagnostic tests that doctors use is a blood test that measures levels of alpha-fetoprotein (AFP). This protein is produced in the liver and can be elevated in liver cancer patients, acting as a sign of tumor growth. However, this test is not without flaws, as 30% of individuals with liver cancer can exhibit normal APF levels. Conversely, APF levels can also be elevated in individuals without liver cancer. Because of this, a firm diagnosis of liver cancer usually involves more invasive procedures such as a biopsy.
While the APF blood test focuses on the level of a single protein, a new blood test examines circulating tumor DNA (cTDNA), which is genetic material that is shed by cancerous tumors. By looking at cTDNA, researchers could look at any number of possible DNA changes in HCC patients versus normal controls. Specifically, they were interested in examining markers of methylation. Methylation is a process that can regulate gene expression and excessive DNA methylation can turn a specific gene off. This is especially critical in cancer, as increased methylation of tumor suppressor genes is an early event in tumor development.
The Nature Materials study discovered that HCC patients had a specific set of methylation markers in their blood, whereas the controls did not. They also found that these methylation markers were very effective at predicting a diagnosis of HCC and an increase in these markers was associated with a later progression of the disease. Strikingly, 40% of HCC patients in the study had normal APF levels, suggesting that measuring methylation patterns may be a more sensitive diagnostic test. This improved blood test is a major step is cancer diagnostics, and provides hope for early detection and improved prognosis for a disease that kills over 700,000 people worldwide each year.
Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma