MULTICENTER ANALYSIS OF SOLUBLE AXL REVEALS DIAGNOSTIC VALUE FOR VERY EARLY STAGE HEPATOCELLULAR CARCINOMA

Background:

Hepatocellular carcinoma (HCC) is the most frequently diagnosed liver malignancy and third most common cause of cancer-related mortality worldwide. If diagnosed at early stages, patients with hepatocellular carcinoma can receive curative therapies, whereas therapeutic options at later stages are very limited.

Material and Methods:

In this study, we show the potential of soluble Axl (sAxl) as a biomarker of early HCC by analyzing levels of sAxl in 311 HCC and 237 control serum samples from centers in Europe and China. sAxl levels were determined using sandwich enzyme-linked immunosorbent assay (R&D Systems Inc., USA).

Results:

Significantly increased median levels of sAxl were found in all HCC (18.575 ng/ ml) as compared to healthy (13.388 ng/ ml) or cirrhotic (12.169 ng/ ml) controls. Receiver operating characteristics curve analysis of sAxl in very early stage HCC patients (BCLC 0) showed an area under the curve (AUC) of 0.848, with a sensitivity of 76.9% and a specificity of 69.2%. A-fetoprotein (AFP) negative HCC patients displayed an AUC of 0.803, with sensitivity and specificity of 73% and 70.8%. Combination of sAxl and AFP improved diagnostic accuracy to 0.936 in very early HCC patients and to 0.937 in all HCC. Differential diagnosis of very early HCC versus liver cirrhosis showed a combined performance for sAxl and AFP of 0.901 with a sensitivity of 88.5% and a specificity of 76.7%. Furthermore, sAxl levels failed to be elevated in primary ovarian, colorectal and breast carcinomas as well as in secondary hepatic malignancies derived from colon.

Conclusions:

In summary, we report high specifity of sAxl in detecting very early HCC, as compared to AFP alone. Combination of sAxl and AFP shows high accuracy in differential diagnosis between HCC and hepatic cirrhosis. sAxl is suggested as a biomarker for routine clinical use.

This study was funded by European Regional Development Fund and State budget of the Czech Republic (RECAMO: CZ 1.05/ 2.1.00/ 03.0101) and by Ministry of Education, Youth and Sports (BBMRI: LM2010004). Published in: Reichl P et al. Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma. Int J Cancer 2014. doi: 10.1002/ ijc.29394.