Diagnostic and prognostic performance of serum GPC3 and PIVKA-II in AFP-negative hepatocellular carcinoma and establishment of nomogram prediction models

作者：Yingying Lin, Yurong Ma, Yan Chen, Yepei Huang, Jinchuan Lin, Zhenzhou Xiao, Zhaolei Cui · 发表于：BMC Cancer · 年份：2025 · DOI：10.1186/s12885-025-14025-y · 被引用次数：9 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer, Lipids, and Metabolism、Inflammatory Biomarkers in Disease Prognosis

OBJECTIVE: A significant proportion, ranging from 20 to 40%, of individuals with hepatocellular carcinoma (HCC) do not exhibit elevated Alpha-fetoprotein (AFP) levels. This study aimed to evaluate the utility of serum glypican-3 (GPC3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) in an AFP-negative HCC (N-HCC) population, and to develop nomogram diagnostic and prognostic prediction models utilizing GPC3 and PIVKA-II. METHODS: Serum GPC3 and PIVKA-II levels were measured in this case-control study, followed by the establishment of a receiver operating characteristic (ROC) curve, restricted cubic spline (RCS), and Kaplan-Meier survival curve. Additionally, a diagnostic prediction nomogram was constructed using univariate and multivariate logistic regression. Furthermore, we utilized least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression to develop a prognostic prediction nomogram. The performance of these models was evaluated using ROC curve analysis and decision curve analysis (DCA). RESULTS: Serum GPC3 and PIVKA-II expression levels were significantly elevated in untreated patients with N-HCC (especially stageI and tumor size < 3 cm) compared to those with AFP-negative benign liver disease (N-BLD). Derived from ROC analysis, the diagnostic cutoff points for GPC3 and PIVKA-II were set at 0.100 ng/mL and 40.00 mAU/mL, respectively. PIVKA-II demonstrated sensitivity and specificity of 84.62% and 90.38%, surpassi...