Study Shows That New Genetic Biomarker Could Be Key to Early Detection--and a Less Costly, More Convenient Test for Patients

Cedars-Sinai Cancer investigators have created a blood test that uses a technology made commonly available during the COVID-19 pandemic to detect the most common form of liver cancer—at an early enough stage that cure is possible. Their work was published online in the peer-reviewed journal Hepatology.

“This important work could fill an unmet need for a more user-friendly, more accurate screening test that detects liver cancer early and saves lives,” said Ju Dong Yang, MD, medical director of the Liver Cancer Program at Cedars-Sinai and a corresponding author of the study.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is usually undetectable until it reaches an advanced stage, when it is usually fatal. It occurs mainly in people with scarring of the liver, called cirrhosis, or chronic hepatitis B infection. There are fewer than 200,000 cases per year in the U.S., but globally it is the third-leading cause of cancer death, and in some countries, it is the most common cancer-related death.

Currently, the best available screening method for at-risk patients is ultrasound imaging of the liver. However, ultrasound testing can be expensive and time-consuming, putting it out of reach of many patients, and the tests often miss smaller, early-stage tumors that could be curable.

“Most at-risk patients aren’t screened,” Yang said. “They struggle to get insurance authorizations and contact the imaging center, and then show up to have the test done—and the test’s accuracy can be limited, particularly in patients with obesity or more advanced liver disease. This is where a screening blood test becomes increasingly valuable.”

The test pioneered by Yang and colleagues is a form of “liquid biopsy” that looks for evidence of cancer in blood specimens and uses polymerase chain reaction (PCR) technology—the same technology used in some tests for COVID-19.

In this study, a Phase II multicenter clinical trial, the team investigated a protein biomarker on the surface of extracellular vesicles, particles that cells use to communicate with each other and which circulate in the blood. The marker proved around 90% accurate in identifying patients with hepatocellular carcinoma. 

“In addition to its excellent performance, this marker has the advantages of being user-friendly, cost efficient, and having a fast turnaround time—within six hours from sample collection to result,” said Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer. “PCR testing technology has been widely deployed during the COVID-19 era, and once this marker has been validated in subsequent studies, it can be easily adopted by existing PCR facilities.”

The test could prove especially lifesaving in parts of the world where imaging resources are limited. To date, no other liquid biopsy test for liver cancer has been evaluated rigorously enough for use in clinical practice, Yang said.

“We’re the first team looking at extracellular vesicles as a detection biomarker for early-stage liver cancer, and our study showed it had outstanding performance,” Yang said. “We are planning on doing larger-scale studies to further validate this test and bring it into routine clinical practice here—and globally.”

Funding: The study was supported by an American College of Gastroenterology Junior Faculty Development Award, Department of Defense Peer Reviewed Cancer Research Program Career Development Award number CA191051, and National Institutes of Health grant numbers R01 CA218356, U01 CA198900, P01 CA233452, R01 CA255727, R01 CA253651, R01 CA246304, U01 CA230705, U01 EB026421, U54 CA14391, R21 CA240887, and R21 CA235340.

Disclosures: Ju Dong Yang, PhD, provides consulting services for Exact Sciences, a company specializing in the detection of early-stage cancers, and the pharmaceutical companies Gilead Sciences and Eisai.