Construction and validation of a predictive model for hepatocellular carcinoma based on serum markers

Background: Early hepatocellular carcinoma (HCC) detection with non-invasive biomarkers remains an unmet clinical need. We aimed to construct a predictive model based on the pre-diagnostic levels of serum markers to predict the early-stage onset of HCC.

Methods: A total of 339 HCC patients (including 157 patients from Changzhou cohort and 182 patients from Wuxi cohort) were enrolled in our retrospective study. Levels of 25 baseline serum markers were collected. Propensity score matching (PSM) analysis was conducted to balance the distributions of patients' gender, age, and the surveillance time between HCC group and control group. Then, Receiver operating characteristic (ROC) and Logistic regression analysis were performed to screen the independent predictive variables and construct a non-invasive predictive model. Subsequently, ROC curve and Kaplan-Meier (K-M) curve were used to evaluate the predictive values of the model. Clinical net benefit of the model was demonstrated by decision curve analysis (DCA) and clinical impact curve.

Results: Five independent predictive variables for HCC onset and two general characteristics of patients (age and gender) were incorporated into the score model. ROC and DCA curves showed that the score model had better predictive performance in discrimination and clinical net benefit compared with single variable or other score systems, with the area under the curve (AUC) of 0.890 (95% CI 0.856-0.925) in Changzhou cohort and 0.799 (95% CI 0.751-0.849) in Wuxi cohort. Meanwhile, stratification analysis indicated that the score model had good predictive values for patients with early tumor stage (AJCC stage I) or small tumors (< 2 cm). Moreover, the score of HCC patient began to increase at 30 months before clinical diagnosis and reach a peak at 6 months.

Conclusion: Based on this model, we could optimize the current risk stratification at an early stage and consider further intensive surveillance programs for high-risk patients. It could also help clinicians to evaluate the progression and predict the prognosis of HCC patients.