Development of a diagnostic nomogram for alpha-fetoprotein-negative hepatocellular carcinoma based on serological biomarkers

Figure 1 Flow chart of the study. HCC: Hepatocellular carcinoma; AFP: Alpha-fetoprotein.

Figure 2 Expression levels of serum biomarkers. A: Serum GP73 expression levels in the alpha-fetoprotein (AFP)-positive hepatocellular carcinoma (HCC) and AFP-negative HCC groups and healthy subjects; B: Log-transformed des-γ-carboxyprothrombin expression levels; C: Log-transformed CK8-M65 expression levels; D: Log-transformed CK8-M30 expression levels (red represents the AFP-positive HCC group, green represents the AFP-negative HCC group, and blue represents the healthy group). HCC: Hepatocellular carcinoma.

Figure 3 Receiver operating characteristic curve for the diagnosis of alpha-fetoprotein-negative hepatocellular carcinoma. A: Receiver operating characteristic (ROC) curve for diagnosing alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients with biomarkers (continuous variable); B: ROC curve for diagnosing AFP-negative HCC patients with biomarkers (converted to dichotomous variables). ROC: Receiver operating characteristic.

Figure 4 Receiver operating characteristic curves and calibration curves of several models. A: The receiver operating characteristic (ROC) curves for Model 1 and Model 2; B: The ROC curves for Model 1 and Model 3; C: The ROC curves for Model 1 and CK18-M65; D: Calibration curves based on Model 1 and the actual observation; E: Calibration curves based on Model 2 and the actual observation; F: Calibration curves based on Model 3 and the actual observation. AUC: Area under the curve.

Figure 5 Construction of the nomogram. A: Random forest method to evaluate the importance of CK18-M65, GP73, DCP, and CK18-M30; B: Diagnostic nomogram for patients with alpha-fetoprotein negative hepatocellular carcinoma (red is the first reference value). ^aP < 0.05.

Figure 6 Performance assessment of the nomogram. A: Decision curve analysis for hepatocellular carcinoma patients. Black line: All patients had the disease. Grey line: Patients with no disease. Red line: Model from the column chart; blue line: CK18-M65; green line: GP73; B: Clinical impact curve analysis. Dashed blue line: Number of disease cases in the high-risk population. Red line: High-risk population.