Serum N-glycan fingerprint helps to discriminate intrahepatic cholangiocarcinoma from hepatocellular carcinoma

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two main types of primary liver cancer, and reliable discrimination is important for optimal treatment. Aberrant glycosylation was detected in HCC and ICC. Both cross-sectional and follow-up studies were performed to establish a differential diagnosis model using N-glycans. A total of 420 participants were enrolled, with 310 patients in training cohort and 110 patients in validation cohort. The follow-up cohort was used to assess the prognosis of ICC. As the results, the diagnostic efficacy of the model was superior to alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) when identifying ICC from HCC (AUC of the nomogram: 0.845, 95%CI: 0.788–0.902; AFP: 0.793, 95%CI: 0.732–0.854; CEA: 0.592, 95%CI: 0.496–0.687; CA 19-9: 0.674, 95%CI: 0.582–0.767) in training cohort. In validation cohort, this model (AUC: 0.810, 95% CI: 0.728–0.891) also demonstrated high efficacy in distinguishing ICC from HCC. Furthermore, the nomogram helps to stratify ICC into two subgroups with high or low risk of survival and recurrence. Therefore, a nomogram integrating six N-glycans NGA2FB(Peak2), NG1A2F (Peak3), NA2 (Peak5), NA2F (Peak6), NA3 (Peak8) and NA4 (Peak11)] was established for ICC and HCC differentiation, and for prognosis assessment in ICC patients.