Biomarker test may speed up primary detection of liver cancer

While EVs are released by normal cells, they are released to a greater extent by tumor cells and cells within a tumor microenvironment. Researchers at the University of California, Los Angeles (UCLA) and other collaborators have developed a simplified surface protein assay (HCC EV SPA) capable of analyzing and quantifying eight subpopulations of HCC EVs .


The use of HCC EVs may enable rapid and inexpensive detection of HCC at an early stage with high sensitivity in at-risk patients with liver cirrhosis, wrote the researchers, including Hsian-Rong Tseng, PhD, expert in molecular and medical pharmacology.


There were more than 30,000 deaths from primary liver cancer in the United States in 2021. HCC accounts for 80% to 85% of primary liver cancers, most commonly occurring in patients with liver cirrhosis or chronic hepatitis B virus infection.


Scientists believe that the sensitivity of current surveillance methods to detect HCC at an early stage is suboptimal. The American Association for the Study of Liver Diseases guidelines recommend that at-risk patients undergo biannual liver ultrasound to detect HCC at a curative stage.


However, the accuracy of ultrasound imaging remains low, with a sensitivity between 60 and 70% and a specificity of 90%, which requires non-invasive tests for early detection.


The scientists’ streamlined HCC EV SPA can quantify eight HCC EV subpopulations in 400 µL plasma samples based on four HCC-associated surface protein markers and two EV markers.


A biostatistical analysis of the resulting HCC EV surface protein signatures establishes an HCC EV ECG score, helping to distinguish early-stage HCC from risky cirrhosis.


The test uses two platform technologies: proprietary clickable beads, also known as methyltetrazine [mTz]-modified microbeads, which purify HCC electric vehicles from a small volume of plasma samples; and real-time multiplex immuno-PCR, which quantifies HCC EV subpopulations.


The researchers developed a statistical model based on the patient’s gender, age, and three serum biomarkers (AFP-L3, AFP, and des-gamma-carboxy prothrombin), which was extremely sensitive in detecting HCC in biomarker studies. phase II, distinguishing early stage cancer from cirrhosis.


After researchers optimized HCC EV SPA using contrived samples and confirmed reproducibility, 45 early-stage HCC patients and 61 at-risk patients with liver cirrhosis entered the phase II study . Age, gender, and ethnicity were similar in HCC patients and cirrhotic controls. About three-quarters of people with HCC had well-compensated liver disease, compared with almost half of cirrhotic controls.


Among patients with HCC, 82% had cirrhosis of the liver. The researchers compared the HCC EV ECG scores of patients with early-stage HCC to those of patients with other cancers. The scores of HCC patients were significantly higher than the scores of patients with other cancers, confirming the specificity of EV HCC ECG scores to HCC rather than to cancers in general.


The score has been validated to accurately detect HCC at an early stage of cirrhosis. According to the researchers, the sensitivity and specificity of the test significantly outperformed serum alpha-fetoprotein and remained consistently excellent throughout the subgroup analyses.


Further validation in a larger multicenter phase II biomarker study and a phase III study are needed to confirm the clinical utility of the test, they added.


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