Monitoring tumor DNA may prove pivotal for early detection of liver cancer


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

2 thoughts on “Monitoring tumor DNA may prove pivotal for early detection of liver cancer”

  1. Just curious – how accurate is the diagnostic test -what was the pt sample size and what was the correlation between HCC diagnosis and a positive methylation score.
    Also what was the range of the methylation score – was there a wide variabilty in metylation levels between hcc and non hcc pts?
    And is the methylation test specific for hcc pts only or can it be used for pts with hcv, hepB, nash, or other liver diseases? Thanks!

    Liked by 1 person

    1. Hi Joey- great questions, and I’ll try to answer them the best I can.

      They actually ran two groups: the first had 715 HCC patients and 560 controls. This first group is where they discovered abnormal methylation patterns. So, to validate they ran their predictive diagnostic model that detects abnormal methylation on a separate group of 383 HCC patients and 275 controls.

      While I couldn’t find an exact correlation value, measuring methylation levels for a HCC diagnosis was very specific (92%) and sensitive (84%). These values are higher than the traditional AFP test

      There was variability in the methylation scores, however, it appeared to be about the same amount for both the control samples and HCC patients. On average, the median methylation score was about 5-8x higher in HCC patients versus controls (depending on the cancer stage).

      They did look at methylation levels in patients with other liver diseases (HBV/HCV infection, and fatty liver). In contrast to HCC patients, patients with other liver diseases did not have differences in methylation patterns versus controls. Thus, it appears that the methylation test may be specific to HCC patients

      Hope I answered your questions and thanks for stopping by NeuroChow


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