SFRP-4, a potential novel serum marker for chronic hepatitis B-related hepatocellular carcinoma

Abstract

The current methods used for diagnosing hepatocellular carcinoma (HCC) are unsatisfactory. Here, we assessed the serum levels of secreted frizzled related protein 4 (sFRP-4) for diagnosing HCC in patients infected with chronic hepatitis B (CHB). In 272 patients with CHB enrolled, 142 were patients with HCC. Thirty-three healthy subjects were recruited as healthy controls. The CHB patients were assigned to a test group or a validation group based on the time of enrollment. Human antibody arrays were used to screen 15 patients (8 CHB-related HCC patients, 7 CHB patients) for serum markers. Four markers and one candidate marker were assessed in the test group and validation group, respectively. Human antibody assays indicated that the serum levels of sFRP-4 in HCC patients were significantly higher than those in CHB patients (P<0.05). Additionally, serum sFRP-4 levels were significantly higher in the HCC patients than those in the non-HCC patients in both test group (79.7 vs 41.3 ng/mL; P<0.001) and validation group (89.0 vs 39.0 ng/mL; P<0.001). Areas under the Receiver Operating Characteristic curves (AUCs) for alpha-fetoprotein (AFP) and sFRP-4 were similar in both test group and validation group. In the test group, the combination of sFRP-4 (a sensitivity of 94.4%, a specificity of 60.5% at 46.4 ng/mL) and AFP (a sensitivity of 75.0%, a specificity of 87.2% at 11.3 ng/mL) showed better performance for diagnosing HCC (a sensitivity of 79.2% and a specificity of 95.3%). The AUC for combined sFRP-4 and AFP increased to 0.941 (95% CI: 0.908-0.975), and similar results were seen in the validation group. sFRP-4 is a candidate serum marker for diagnosing HCC in CHB patients, and the combination of sFRP-4 with AFP may improve the diagnostic accuracy of HCC.