Diagnostic Value of Serum Biomarkers in Combined Hepatocelluar-Cholangiocarcinoma

Objective: To explore the value of des-gamma-carboxyprothrombin (DCP), alpha-fetoprotein (AFP) and carbohydrate antigen-199 (CA-199) for diagnosis of combined hepatocellular-cholangiocarcinoma (cHCC-CC). Study Design: Observational correlational study design. Place and Duration of Study: The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from June 2016 to June 2019. Methodology: Patients with cHCC-CC (n = 26) diagnosed by histological examination and immunohistochemical staining were matched as 1:2 to controls (n = 52) based on age (+/- 2 years), gender (male or female), liver texture (cirrhosis or not) and ethnicity. Serum DCP, AFP and CA-199 levels were determined and Youden indices were calculated. Receiver operating characteristic (ROC) curves were generated and areas under the receiver operating characteristic curve (AUC) were calculated. Results: The levels of DCP, AFP and CA-199 were clearly elevated in the cHCC-CC group relative to controls with p-values of <0.001, <0.001 and 0.001, respectively. Youden index values for DCP, AFP, CA-199, and their combination (DCP+AFP+CA-199) were 0.5, 0.423, 0.173 and 0.673, respectively. The AUC curve values for DCP, AFP, CA-199 and their combination (DCP+AFP+CA-199) were 0.759 (95% CI: 0.624 - 0.894), 0.826 (95% CI: 0.720 - 0.933), 0.727 (95% CI: 0.613 - 0.841) and 0.862 (95% CI: 0.755 - 0.968), respectively. Conclusion: DCP, AFP and CA-199 have diagnostic value for cHCC-CC, and the combination of DCP, AFP and CA-199 is useful for assisting diagnosis before histological examination. Clinicians should be alert for cHCC-CC when DCP, AFP, or CA-199 levels are abnormal.