Diagnosing Liver Cancer

THEN 

For centuries, it simply wasn’t feasible to diagnose a liver tumor until a patient was close to death. Physicians were confined to the tools at their disposal — visual examination, palpation and dissection.

Angiography, a diagnostic procedure that uses X-ray images to look for blockages or narrow spots in blood vessels, was a conventional liver cancer diagnostic tool in the 1950s and 1960s. By the early 1970s, ultrasound was developed as a tool, followed by CT and MRI in the early 1980s.

Alpha-fetoprotein (AFP), the first biomarker for liver cancer, was discovered in 1963 and became a game changer for screening protocols. By the 1980s, AFP was being combined with angiography and ultrasound to monitor high-risk patients. 

NOW

Unfortunately, it remains very difficult to diagnose liver cancer in its early stages. Doctors typically still rely on tests such as angiogram, blood tests, CT scan, liver ultrasound and MRI.

Current liver cancer screenings measure how much AFP protein is in our blood. When elevated, the test serves as a good indicator that someone has liver cancer. However, about half of people with liver cancer do not have elevated AFP, which results in a false negative test and subsequently later diagnoses at more advanced stages. This is a critical need because liver cancer can be highly treatable in its early stages but becomes extremely difficult to manage in later stages. 

NEXT

Funded in part by VeloSano, Cleveland Clinic’s cancer research fundraising movement, two Cleveland Clinic researchers recently discovered biomarkers with potential to dramatically improve early liver cancer detection.

Courtney Hershberger, PhD, and Noah Daniels, PhD, working in the lab of Daniel Rotroff, PhD, used a different approach to analyze existing data from patient blood samples. The process, known as alternative splicing, is often overlooked because it requires deep, specialized knowledge.

Alternative splicing describes how our cells cut and process RNA from one gene to make multiple versions of a protein. Depending on how those pieces are combined, one gene can produce proteins with different functions.

Dr. Hershberger identified splicing patterns in the blood that could distinguish between individuals with liver cancer and those with other liver diseases. Adding her splicing biomarkers to the standard AFP diagnostic test significantly improved early liver cancer detection, catching about 50% more cases. Meanwhile, Dr. Daniels’ study identified splicing markers in white blood cells that detected nearly all (93%) liver cancer cases and 81% of early cases — a dramatic increase from the 50% success rate of AFP tests.

The next step? Validating these biomarkers for use in patient care. With continued funding, Cleveland Clinic scientists will keep working to find ways to diagnose liver cancer sooner and create hope for patients.