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Extracellular Vesicle–Based Protein Assay May Enable Earlier Detection of Hepatocellular Carcinoma

By: Celeste L. Dixon
Posted: Wednesday, December 7, 2022

Biomarker-based technology in development might detect early-stage hepatocellular carcinoma with better sensitivity than currently available methods, according to research published in Hepatology. According to Hsian-Rong Tseng, PhD, of Jonsson Comprehensive Cancer Center, University of California, Los Angeles, and colleagues, at least one of four types of protein biomarkers—EpCAM, CD147, GPC3, and ASGPR1—may be present in almost all hepatocellular carcinoma tissue. The team used the data about these markers to create the Hepatocellular Carcinoma Extracellular Vesicles Surface Protein Assay and accompanying score. In the final assay, EpCAM, CD147, and GPC3 were denoted as the assay score, as ASGPR1 did not offer sufficient diagnostic performance.

Extracellular vesicles are circulating biomarkers that can be checked with microarray staining for those protein biomarkers. The vesicles also contain other biomolecules, including DNA, RNA, metabolites, and lipids, and are enclosed by lipid bilayer membranes. Although extracellular vesicles are also released by healthy cells, the significance of those released by tumor cells is that they are present early in tumorigenesis.

The score is calculated from the readouts of three of the hepatocellular carcinoma extracellular vesicle subpopulations (EpCAM+ CD63+, CD147+ CD63,+ and GPC3+ CD63+) to detect early-stage hepatocellular carcinoma. The investigators undertook a phase II biomarker study to evaluate the score’s performance in a training cohort (n = 106) and an independent validation cohort (n = 72). Virtually all (99.7%) of the tissue microarrays stained positive for at least one of the types of protein biomarkers, which translated into a sensitivity of 91% and a specificity of 90% in distinguishing early-stage hepatocellular carcinoma from cirrhosis.

Currently, the recommended screening for patients at high risk for hepatocellular carcinoma is biannual ultrasound imaging, with or without serum alpha-fetoprotein analysis. However, the sensitivity of those tests for detecting the disease at a curative stage is between 60% and 70%, reported Dr. Tseng and co-investigators. The team plans to test further the two platform technologies they developed to bring better testing to that at-risk population, composed mostly of adults with liver cirrhosis or chronic hepatitis B virus.

Disclosure: The study authors’ disclosure information can be found at

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