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Serum Outperforms Plasma for Glypican-3 Quantification in Hepatocellular Carcinoma-A Prospective Comparative Study
Ming-Tze Yang1, Jiunn-Min Wang2, Chen-Shiou Wu3
1Department of International Medical Service Center, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung 40705, Taiwan.
Journal of Clinical Medicine
|January 28, 2026
Summary
Serum is the preferred matrix for Glypican-3 (GPC3) measurement in hepatocellular carcinoma (HCC) diagnostics due to its superior stability and diagnostic accuracy compared to plasma, especially under frozen conditions.
Area of Science:
- Biochemistry
- Oncology
- Clinical Diagnostics
Background:
- Glypican-3 (GPC3) is a biomarker frequently overexpressed in hepatocellular carcinoma (HCC).
- Optimal specimen matrix (plasma vs. serum) for GPC3 measurement remains unclear.
- This study addresses the gap in understanding GPC3 stability and diagnostic utility across different matrices.
Purpose of the Study:
- To compare the stability and diagnostic performance of Glypican-3 (GPC3) in serum versus plasma.
- To determine the optimal specimen matrix for GPC3 measurement in hepatocellular carcinoma (HCC) detection.
- To evaluate the impact of storage conditions on GPC3 concentrations.
Main Methods:
- Prospective enrollment of 100 participants (healthy controls, chronic liver disease, HCC patients).
- Analysis of paired serum and plasma samples under fresh and stored conditions (7 days at 4°C and -70°C).
- Comparison of GPC3 concentrations, correlation, and diagnostic accuracy (AUROC) between matrices and conditions.
Main Results:
- Fresh plasma showed higher GPC3 levels than serum, but plasma GPC3 significantly declined after storage.
- Serum GPC3 levels remained stable across fresh and all storage conditions.
- Both matrices discriminated HCC, but serum exhibited superior diagnostic performance (AUROC 0.836 vs. 0.772) under -70°C storage.
Conclusions:
- Serum offers superior stability for Glypican-3 (GPC3) measurement compared to plasma.
- Serum demonstrates enhanced diagnostic accuracy for hepatocellular carcinoma (HCC) detection under frozen storage.
- Serum is recommended as the preferred specimen matrix for clinical and research applications involving GPC3.
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