Biomarker to distinguish hepatocellular carcinoma from cholangiocarcinoma by serum a disintegrin and metalloprotease 12

INTRODUCTION: The “a distintegrin and metalloprotease” (ADAM) family contributes to regulation of the cell-cell and cell-matrix interaction that are critical determinants of malignancy. It also plays important roles in the degradation of the basement membrane during tumor invasion. To evaluate a distinguishing biomarker for hepatocellular carcinoma from cholangiocarcinoma, a disintegrin and metalloprotease 12 (ADAM12) level was determined. MATERIAL AND METHODS: The indirect ELISA and Western blot analysis for quantification of ADAM12 level in serum was developed. The subjects were 218 histologically confirmed cases, 128 with intrahepatic cholangiocarcinoma, 30 with hepatocellular carcinoma and 60 healthy people. RESULTS: The ability of test was verified using an analysis of Receiver Operating Characteristic (ROC) curve. The mean value of serum ADAM 12 in hepatocellular carcinoma was significantly higher than cholangiocarcinoma and healthy people (p = 0.001). The AUC for control vs. HCC was 0.826 while for controls vs. CC was 0.679. The results showed that a disintegrin and metalloprotease 12 for hepatocellular carcinoma had better specificity (77.4%) than for cholangiocarcinoma (64.5%). The serum a disintegrin and metalloprotease 12 level was also found to inversely correlate with overall survival (p = 0.02). CONCLUSIONS: A disintegrin and metalloprotease 12 would be most useful as an adjunct biomarker for distinguishing hepatocellular carcinoma from cholangiocarcinoma.