Researchers identify biomarkers in blood to predict liver cancer risk — Harvard Gazette (2024)

A new study suggests that proteins detectable in the blood could improve predictions about risk of liver cancer, which is typically diagnosed at later stages when survival rates are lower.

Led by investigators at Harvard-affiliated Beth Israel Deaconess Medical Center and Mass General Brigham, the team’s results are published in JNCI.

Liver cancer, or hepatocellular carcinoma (HCC), ranks as the third leading cause of cancer worldwide and the second leading cause of cancer-related deaths globally, with its incidence rate steadily increasing. Detection of liver cancers often occurs at advanced stages, when life expectancy typically spans less than 12 months. Currently, there is a notable deficiency in accurate, sensitive, and specific tools for the early detection of liver cancer. Many existing methods are relatively expensive, invasive, or limited in accessibility, primarily confined to major hospitals.

“Liver cancer rates are rapidly increasing, and liver cancer has a high mortality rate, but if we can diagnose it early, therapeutic interventions can be potentially curative.”

Xinyuan Zhang, BWH

The team used proteomics, the study and profiling of proteins, to develop a minimally invasive model for diagnosing or screening for liver cancer at an earlier, more treatable stage. Using the SomaScan Assay Kit — a high-throughput proteomics platform that measures protein levels in biological samples, available through BIDMC’s Genomics, Proteomics, Bioinformatics and Systems Biology Center — the investigators detected 1,305 biologically relevant proteins that may be present in the blood at early stage of disease.

“Liver cancer rates are rapidly increasing, and liver cancer has a high mortality rate, but if we can diagnose it early, therapeutic interventions can be potentially curative,” said lead author Xinyuan (Cindy) Zhang of the Channing Division of Network Medicine at Brigham and Women’s Hospital. “We need to have a way to detect this form of cancer early enough to intervene with surgery or liver transplantation to treat the disease before it becomes metastatic.”

The study team used SomaScan to analyze plasma samples from participants in both the Nurses’ Health Study and the Health Professional Follow-Up Study, two longitudinal, ongoing, prospective cohorts in the U.S. Notably, they examined blood samples obtained from patients an average of 12 years before their liver cancer diagnosis to pinpoint protein biomarker signals. After examination, the researchers cross-referenced medical records to confirm whether these patients ultimately developed liver cancer.

From the blood samples, the researchers identified 56 plasma proteins that showed significantly elevated levels in patients with liver cancer compared to matched control samples without HCC. The team selected four of these proteins to create a predictive model, which they tested on the U.K. Biobank Pharma Proteomics dataset, comprised of 50,000 individuals, 45 of whom were diagnosed with liver cancer. Their model had greater accuracy in predicting liver cancer compared to traditional risk factors.

The authors caution that their study included a limited number of liver cancer cases and further validation in larger, more diverse patient populations and in high-risk populations is needed.

“It’s always been challenging to identify highly specific disease biomarkers in the blood using traditional tools, but new technology allows us to detect a broad and dynamic range of both high and low abundant proteins,” said co-senior author Towia A. Libermann of the division of Interdisciplinary Medicine and Biotechnology at BIDMC. “New insights into the biological mechanisms underlying liver cancer development emerge from our data that may lead to identification of novel therapeutic targets. Most importantly, we were able to validate these early detection biomarkers using alternative protein analysis techniques and in an independent population cohort from the U.K.”

The study team aims to extend their methodology to uncover additional plasma protein biomarkers, explore biomarkers linked with different cancer types, and gain deeper insights into the role of HCC risk factors across specific patient populations. With further progress, the protein biomarkers investigated in the study could potentially hold clinical significance as a non-invasive test for assessing liver cancer risk.

“Even though further investigation in additional populations is needed, our results reveal a robust circulating protein profile associated with liver cancer years before diagnosis, which is truly remarkable,” said co-senior author Xuehong Zhang, who conducted work on this study while at the Channing Division of Network Medicine at the Brigham. Zhang is now at Yale

Additional authors include Long H. Ngo, Simon T. Dillon, Xuesong Gu and Michelle Lai, of BIDMC; Longgang Zhao of BWH; Tracey G. Simon and Andrew T. Chan of MGH; and Edward L. Giovannucci of the Harvard T.H. Chan School of Public Health.

This study was supported by the National Institutes of Health (NIH)/National Cancer Institute (NCI) through grants R21 CA238651. Andrew T. Chan served as a consultant for Bayer Pharma AG, Pfizer Inc., and Boehringer Ingelheim for work unrelated to this topic. He has also received grant support from Pfizer Inc., Zoe Ltd, and Freenome for work unrelated to this topic.

Researchers identify biomarkers in blood to predict liver cancer risk — Harvard Gazette (2024)

FAQs

What biomarkers are used for liver cancer detection? ›

Combined use of biomarkers for early detection of liver cancer is prevalent. AFP, DPC and AFP-l3 biomarkers are usedin combination every six months for liver cancer detection (96). Recent studies introduced novel biomarkers for accurate diagnosis and early treatment of liver cancer such as AFU, GP73 and OPN.

What are the blood markers for liver cancer? ›

Alpha-fetoprotein blood (AFP) test

AFP is a protein that can be found in high levels in adults with liver disease, liver cancer, who are pregnant, or other cancers. If AFP levels are very high in someone with a liver tumor, it can be a sign that liver cancer is present.

What are circulating biomarkers for early detection of hepatocellular carcinoma? ›

The experimental results prove that the circulating miRNA-483-5p, 21, and 155 could be novel early diagnostic and prognostic biomarkers for detecting HCC.

Which of the following tests is the most accurate for diagnosing liver cancer? ›

For most types of cancer, a biopsy is the only sure way for the doctor to know whether an area of the body has cancer. In a biopsy, the doctor takes a small sample of tissue for testing in a laboratory.

What is the new biomarker for liver disease? ›

"The soluble form of TREM2 is an excellent biomarker for identifying and staging advanced liver disease, which can progress from fatty liver disease to incurable cirrhosis if left untreated," explains first author Tim Hendrikx from MedUni Vienna's Department of Laboratory Medicine.

What is the best marker for liver disease? ›

Serum albumin test.

This test is used to measure the level of albumin (a protein in the blood) and may be useful in the diagnosis of liver disease. Low levels of albumin may indicate the liver is not functioning properly.

How accurate is blood test for liver cancer? ›

Blood tests alone cannot diagnose liver cancer, but they can help doctors work out what type of liver cancer may be present and how well the liver is working. Blood tests can also provide information on the type of liver disease that may be causing cirrhosis.

Who is most likely to get liver cancer? ›

The most common type of liver cancer in adults, hepatocellular carcinoma (HCC), typically develops in people with chronic (long-lasting) liver disease caused by hepatitis virus infection or cirrhosis. Men are more likely to develop HCC than women. People with multiple risk factors have an even higher risk.

What levels are elevated with liver cancer? ›

Alpha-Fetoprotein Testing

An elevated AFP level can be a sign of liver cancer, but not always. If liver cancer is present, high AFP levels can mean the condition has spread.

What is the most sensitive marker for HCC? ›

AFP mRNA. AFP mRNA is considered the most valuable marker for circulating HCC cells and is only present in active HCC cells. If other interferences such as genital tumors and peripheral blood are excluded, AFP mRNA could be used as a significant marker for spreading of HCC in blood.

What is the biomarker for liver function test? ›

The liver function tests typically include alanine transaminase (ALT) and aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), serum bilirubin, prothrombin time (PT), the international normalized ratio (INR), total protein and albumin.

What is the most useful circulating marker for patients with hepatocellular carcinoma? ›

Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma, and has been proven to have capability of prefiguring the prognosis.

What is the gold standard for diagnosing liver cancer? ›

Computed Tomography

Triple-phase CT (including an arterial phase, a portal venous phase, and a late washout phase) has been found to be highly accurate in the diagnosis and characterization of HCCs but, like US, may miss smaller lesions.

What is the gold standard test for liver cancer? ›

Imaging is a non-invasive option compared to traditional tissue biopsy, and MRI is the gold standard for imaging of HCC due to its diagnostic accuracy and significantly higher sensitivity, as well as significantly lower negative likelihood ratio as compared to CT [26].

What does liver cancer pain feel like? ›

Pain from liver cancer can occur in the upper right abdomen, the right shoulder, or the back. The pain may vary depending on the cause. Soft tissue pain may feel pulsating, whereas nerve pain can be sharp or stabbing. In cases where tumors metastasize to bone, a person may experience deep, dull pain.

Are AST and ALT elevated in liver cancer? ›

A high level of AST in the blood may be a sign of liver damage or disease. Alanine aminotransferase (ALT) is an enzyme found in the liver and kidneys. A high level of ALT in the blood is often found before symptoms of liver damage, such as jaundice, develop.

What is a normal liver tumor marker level? ›

AFP tumor marker normal range

AFP is measured in nanograms per milliliter (ng/mL), with normal levels less than 20 ng/mL. Levels above 400 ng/mL may indicate a liver tumor or other cancer. Elevated levels of AFP may indicate cancer of the liver, ovaries or testicles, but that isn't always the case.

Can labs detect liver cancer? ›

A platelet count can detect liver cancer in its early stages. A white cell count below the normal range can be a sign of an enlarged spleen (splenomegaly) and/or an increase in the blood pressure within the liver's blood vessels (portal hypertension).

References

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