Unique sugar structures could identify early-stage liver cancer

Medical University of South Carolina (MUSC) researchers report in Molecular Cancer Research that they have identified specific sugar structures that correlate to different subtypes of hepatocellular carcinoma, the most common form of liver cancer. The ability to distinguish hepatocellular carcinoma subtypes could lead to earlier detection and more targeted therapies for the disease.

Only about 8% of patients with hepatocellular carcinoma survive, in part because their disease was not detected early, when surgery or chemotherapy might have been more effective. Screening for hepatocellular carcinoma currently relies on a single biomarker, which may not be relevant to all subtypes, meaning that many cases could be missed.

“We have been thinking about all liver cancers as being the same and using the same diagnostic tool for everyone,” explained Anand Mehta, Ph.D., senior author on the article and professor in the MUSC Department of Cell and Molecular Pharmacology and Experimental Therapeutics. “And that’s a huge limitation in early diagnosis. It’s the biggest hurdle right now.”

Diagnostic tools that are better able to distinguish between hepatocellular carcinoma subtypes would aid in earlier detection and could lead to more personalized therapies. This approach is already being used for breast and other cancers, and Mehta thinks it could work for liver cancer as well.

In the current study, he and his team, which had previously studied sugar structures in hepatocellular carcinoma tumors, tried to find a way to correlate specific sugar structures to specific hepatocellular carcinoma tumor subtypes.

Around 60% of proteins in the human body contain sugars. These specific sugars, N-glycans, change in a cancerous environment. For example, imagine you are deciding which outfit to wear based on the temperature outside. In normal tissue, the proteins are “decorated” with specific sugars, e.g., a thick coat for winter weather. In a tumor, regardless of the environment, the proteins are decorated with sugars at random, e.g., a thick coat and a beanie for summer weather. Mehta and his lab used these specific “outfits” to distinguish the three genetic subtypes of hepatocellular carcinoma.

“This is the first piece of evidence to show that the genetic subtypes of cancers affect the sugar profile you will see,” said Andrew DelaCourt, a doctoral candidate in the Mehta laboratory and lead author on the article.

DelaCourt thought it particularly interesting that the biomarker currently used to screen for hepatocellular carcinoma is able to detect only one of the two aggressive subtypes that the team studied, lessening the likelihood that the disease would be detected early in people with that subtype. The researchers found that a particular sugar, fucose, is associated with the other aggressive subtype and could be used as an early-detection biomarker.

For this study, Mehta and DelaCourt identified sugars on hepatocellular carcinoma tumors, using a technique pioneered at MUSC that relies on the advanced imaging technology MALDI-IMS, which works by determining the mass of the sugars that are cleaved from a tissue sample. With that information, Mehta’s laboratory was able to identify which sugars correlated with which subtype of hepatocellular carcinoma tumor.

Moving forward, the team wishes to expand this research by investigating whether they can identify hepatocellular carcinoma subtypes using patient blood samples. A blood-based diagnostic would have several clinical advantages. It would be much less invasive, as it would not require patients to undergo a tumor biopsy. It could also be more easily interpreted, as sugar levels in blood can be assessed with widely available techniques.

“The goal is to analyze the similarity between the sugars’ changes in the blood and the tumor tissues,” said Mehta. “This is the next step toward clinical relevance.”

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About MUSC

Founded in 1824 in Charleston, MUSC is the oldest medical school in the South as well as the state's only integrated academic health sciences center with a unique charge to serve the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and nearly 800 residents in six colleges: Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy. The state's leader in obtaining biomedical research funds, in fiscal year 2019, MUSC set a new high, bringing in more than $284 million. For information on academic programs, visit musc.edu.

As the clinical health system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest quality patient care available while training generations of competent, compassionate health care providers to serve the people of South Carolina and beyond. Comprising some 1,600 beds, more than 100 outreach sites, the MUSC College of Medicine, the physicians' practice plan and nearly 275 telehealth locations, MUSC Health owns and operates eight hospitals situated in Charleston, Chester, Florence, Lancaster and Marion counties. In 2020, for the sixth consecutive year, U.S. News & World Report named MUSC Health the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit muschealth.org.

MUSC and its affiliates have collective annual budgets of $3.2 billion. The more than 17,000 MUSC team members include world-class faculty, physicians, specialty providers and scientists who deliver groundbreaking education, research, technology and patient care

About MUSC Hollings Cancer Center

MUSC Hollings Cancer Center is a National Cancer Institute-designated cancer center and the largest academic-based cancer research program in South Carolina. The cancer center comprises more than 100 faculty cancer scientists and 20 academic departments. It has an annual research funding portfolio of more than $44 million and a dedication to reducing the cancer burden in South Carolina. Hollings offers state-of-the-art diagnostic capabilities, therapies and surgical techniques within multidisciplinary clinics that include surgeons, medical oncologists, radiation therapists, radiologists, pathologists, psychologists and other specialists equipped for the full range of cancer care, including more than 200 clinical trials. For more information, visit hollingscancercenter.musc.edu.