Liver cancer could be detected earlier using liquid biopsy

Written by Sarah Jones, Future Science Group

A new diagnostic and prognostic test for the early detection of hepatocellular carcinoma (HCC) has been developed by researchers at the University of California San Diego School of Medicine and Moores Cancer Center (CA, USA), with colleagues at Sun Yet-Sen University Cancer Center (Guangdong Sheng, China) and other collaborating institutions. The method utilizes a blood sample containing circulating tumor DNA (ctDNA). The results appear in the October 9 issue of Nature Materials.

HCC, which is among the leading causes of cancer mortality in the world, results in 740,000 deaths each year with more than 780,000 new cases. The incidence rates of liver cancer are rising.

“HCC and its precursor, non-alcoholic steatohepatitis, have increased markedly during the past decade and disproportionally affect Hispanic males,” commented Scott Lippman, (Moores Cancer Center). “California has one of the highest rates of liver cancer in the US. This novel report has major implications locally and globally on this devastating disease. It’s also the first report to support the potential of ctDNA for early detection for any cancer.”

As with many cancers, prognosis and survival rates are improved by early detection. This is partly because this allows for the use of localized treatment versus systemic treatments. Currently, detection of HCC relies primarily on imaging and a blood test for alpha-fetoprotein, which is a non-specific tumor marker and is usually elevated when the disease is significantly advanced.

“Non-invasive blood tests or liquid biopsies present a better alternative,” explained Kang Zhang, (Institute for Genomic Medicine and Institute of Engineering in Medicine CA, USA). “However, there has been little success in developing effective blood-based methods for screening HCC. The only blood test, for alpha-fetoprotein , has limited clinical utility due to low sensitivity.”

Liquid biopsies work by detecting fragments of genetic material shed into the blood by tumor cells known as circulating tumor DNA. These biopsies have advantages over traditional tumor detection methods, including the fact that they are minimally invasive and can be carried out at any time during therapy. This could allow physicians to track molecular changes to tumors in real time and get an idea of the entire molecular picture of a patient’s malignancy, rather than just the tested portion of the tumor.

Hundreds of thousands of methylation profiles of HCC patients and healthy controls were examined by Zhang and colleagues. A specific panel of methylation markers that correlated to HCC were then identified. Machine learning and statistical methods were utilized to examine their efficacy at detecting and assessing HCC in 1098 HCC patients and 835 normal controls.

“Our results were very encouraging,” concluded Zhang. “In a large clinical cohort, our blood-based HCC diagnosis highly correlated with tumor burden, treatment response and stage of cancer. Right now, oncologists are quite limited in how they detect HCC and evaluate treatment. Our study is a great demonstration of proof-of-concept for a new, more effective approach that applies to solid malignancies, HCC and beyond.”

Sources: Xu R-H, Wei W, Krawczyk M et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat. Mater. doi:10.1038/nmat4997 (Epub ahead of print) (2017); www.eurekalert.org/pub_releases/2017-10/uoc–lbm100517.php