Article Highlight | 5-Jun-2023

A better biomarker for an aggressive and fatal liver cancer

Medical University of South Carolina team finds a new, more specific biomarker for a liver cancer type. Currently, no specific diagnostic tools of this type exist for this disease.

Medical University of South Carolina

Finding cancer quickly is key in securing the best possible outcome for the patient.

An MUSC research team has found a way to make a lethal type of liver cancer more easily detectable. The team was led by Anand Mehta, D.Phil., Smart State Chair in Proteomic Biomarkers, and Shaaron Ochoa-Rios, Ph.D., who did her doctoral research in the Mehta lab. They report their findings in a recent issue of Cancer Research Communications.

Mehta and Ochoa-Rios identified a biomarker specific to intrahepatic cholangiocarcinoma (iCCA), a lethal type of liver cancer.

CCA is a subtype of the second most common type of liver cancer. It is aggressive and deadly and, if diagnosed late, has a five-year survival rate of only around 8%.

When caught early, however, the prognosis is much better. If the tumor is spotted in the early stages and surgically removed, the five-year survival rate soars to 50%.

“Early detection saves lives,” said Mehta. “If you identify patients who have early-stage cancers, no matter what the cancer, they tend to have much longer survival time.”

However, identifying CCA can be challenging.

The main symptoms of CCA – jaundice, itchy skin, fatigue and abdominal pain – are also common among other liver diseases. It is impossible to tell if people experiencing these symptoms have liver cancer or some other liver issue, said Ochoa-Rios.

Making matters worse, the number of liver cancer cases is likely to increase.

Historically, the 2- to 5 million people who develop liver cirrhosis are at the highest risk of developing liver cancer, said Mehta.

However, two other conditions, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, both associated with a high-fat diet and a sedentary lifestyle, are on the rise and put people at risk for developing liver cancer.

“Almost 100 million people fall into that category,” Mehta said.

Given those numbers, it is not possible to put every single at-risk person through the battery of tests required to detect CCA, he said. Imaging tests are also time consuming, making their large-scale use impractical.

In situations like these, a specific and reliable biomarker is ideal.

Biomarkers

A biomarker is any noninvasive measurement that can be used to give care providers information about a patient’s health. This could be anything from a blood pressure reading to the amount of a substance present in a person’s blood.

The current biomarker used to detect CCA, CA 19-9, is not very specific, explained Ochoa-Rios.

“That same marker is also used to diagnose other types of liver conditions and even other types of cancers as well,” she said.

Because a positive CA 19-9 test doesn’t necessarily mean that a person has iCCA, he or she must also undergo general imaging tests such as MRI or CT scans. This battery of tests takes crucial time and can delay diagnosis and treatment.

Mehta and Ochoa-Rios found a biomarker specific to CCA that could help to speed up diagnosis.

“We believe we have identified a novel serum biomarker of CCA,” said Mehta.

In tissue samples from patients with CCA, Mehta and Ochoa-Rios found certain changes to a type of sugar called N-glycan, which is found on proteins.

It is not known why these N-glycan changes occur, but they seem to occur consistently in tissue with CCA but not in healthy tissue or tissue with other types of liver cancer.

Mehta and Ochoa-Rios also found that they could see these N-glycan changes in blood samples. In fact, they could detect these N-glycan changes by looking at a blood sample just as well as they could by looking at tissue.

This means that these N-glycan changes in the blood function as a biomarker, allowing for the detection of CCA without the need for invasive tissue biopsy.

Additionally, unlike CA 19-9, this new biomarker can help to rule out other diseases.

“This biomarker can distinguish a patient who has cancer from a patient who has a very advanced stage of liver disease, such as cirrhosis,” Ochoa-Rios said.

“The new N-glycan-based biomarker far exceeded the performance of the currently used biomarker,” Mehta explained.

Going forward

Due to the way new biomarkers are rolled out for use in a clinical setting, it will be a while before this new biomarker is widely used. However, Mehta and Ochoa-Rios’ efforts are a foundational step in this process.

The team plans to investigate further the N-glycan changes as well. N-glycans are attached to proteins. It will be important to understand which proteins are associated with N-glycan changes and why.

“We have no idea what proteins have this sugar, and we know historically that a better biomarker is when you have both pieces of information,” said Mehta.

Both Mehta and Ochoa-Rios emphasized the need for a better biomarker for CCA as well as the promise of the N-glycan-based biomarker they found.

“I think as researchers, we are moving in the right direction,” said Ochoa-Rios. “We are trying to address limitations that are present in the clinic.”

“While there is still much work to be done, this is a good start, and we know what directions to take to find a good biomarker for CCA,” said Mehta.

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About MUSC

Founded in 1824 in Charleston, MUSC is the state’s only comprehensive academic health system, with a unique mission to preserve and optimize human life in South Carolina through education, research and patient care. Each year, MUSC educates more than 3,200 students in six colleges – Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy – and trains more than 900 residents and fellows in its health system. MUSC brought in more than $298 million in research funds in fiscal year 2022, leading the state overall in research funding. MUSC also leads the state in federal and National Institutes of Health funding, with more than $220 million. For information on academic programs, visit musc.edu.

As the health care system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest-quality and safest patient care while educating and training generations of outstanding health care providers and leaders to serve the people of South Carolina and beyond. Patient care is provided at 16 hospitals (includes owned and equity stake), with approximately 2,700 beds and four additional hospital locations in development; more than 350 telehealth sites and connectivity to patients’ homes; and nearly 750 care locations situated in all regions of South Carolina. In 2022, for the eighth consecutive year, U.S. News & World Report named MUSC Health University Medical Center in Charleston the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit muschealth.org.

MUSC has a total enterprise annual operating budget of $5.1 billion. The nearly 26,000 MUSC family members include world-class faculty, physicians, specialty providers, scientists, students, affiliates and care team members who deliver groundbreaking education, research, and patient care.

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