Abstract
BACKGROUND AND AIMS: HCC poses a significant global health burden, with HBV being the predominant etiology in China. However, current diagnostic markers lack the requisite sensitivity and specificity. This study aims to develop and validate serum N-glycomics-based models for the diagnosis and prognosis of HCC in patients with chronic hepatitis B-related cirrhosis. APPROACH AND RESULTS: This study enrolled a total of 397 patients with chronic hepatitis B-related cirrhosis and HCC for clinical management. N-glycomics profiling was conducted on all participants, and clinical data were collected. First, machine learning-based models, Hepatocellular Carcinoma Glycomics Random Forest model and Hepatocellular Carcinoma Glycomics Support Vector Machine model, were established for early screening and diagnosis of HCC using N-glycomics. The AUC values in the validation set were 0.967 (95% CI: 0.930-1.000) and 0.908 (0.840-0.976) for Hepatocellular Carcinoma Glycomics Random Forest model and Hepatocellular Carcinoma Glycomics Support Vector Machine model, respectively, outperforming AFP (0.687 [0.575-0.765]) and Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) (0.665 [0.507-0.823]). It also showed superiority in subgroup analysis and external validation. Calibration and decision curve analysis also showed good predictive performance. Additionally, we developed a prognostic model, the prog-G model, based on N-glycans to monitor recurrence in patients with HCC after curative treatment. During the follow-up period, it was observed that this model correlated with the clinical condition of the patients and could identify all recurrent HCC cases (n=12) prior to imaging findings, outperforming AFP (n=7) and PIVKA-II (n=9), while also detecting recurrent lesions earlier than imaging. CONCLUSIONS: N-glycomics models can effectively predict the occurrence and recurrence of HCC to improving the efficiency of clinical decision-making and promoting the precision treatment of HCC.