Serological tumor markers of hepatocellular carcinoma: a meta-analysis

The clinical value of serum α-fetoprotein (AFP) to detect hepatocellular carcinoma (HCC) has been questioned due to its low sensitivity and specificity. Other than AFP, several new serum biomarkers including glypican-3 (GPC3), des-γ-carboxy prothrombin (DCP), α-L-fucosidase enzyme (AFU) and vascular endothelial growth factor (VEGF) have been identified as useful HCC markers.

A systematic search on PubMed, Web of Science and others was performed. Twenty-six case-control studies on HCC-related biomarkers published from 2000 to 2014 were included in this analysis. Data on sensitivity and specificity of tests were extracted and analyzed using the Meta-DiSc 1.4 statistical program. Fixed or random-effects models were used depending on the absence or presence of significant heterogeneity. Summary receiver operating characteristic (sROC) curves were obtained to evaluate the accuracy of the studied markers.

The areas under the sROC curve of AFP, GPC3, DCP, AFU, VEGF and the combination of each of the last 4 markers with AFP were 0.869, 0.928, 0.832, 0.851, 0.834, 0.964, 0.972, 0.873 and 0.948, respectively. A combination of AFP+GPC3, AFP+DCP or AFP+VEGF was superior to AFP alone in detecting HCC. The area under the sROC curve of GPC3 alone was significantly higher than that of AFP, whereas the areas of DCP, AFU and VEGF were comparable to that of AFP.

GPC3, DCP, AFU and VEGF are suitable markers for HCC, and their determination with AFP may prove to be useful in the diagnosis and screening of HCC.