Identification of beta2-microgloblin as a candidate for early diagnosis of imaging-invisible hepatocellular carcinoma in patient with liver cirrhosis.

Glypican-3 (GPC3) is overexpressed in hepatocellular carcinoma (HCC) but not in chronic hepatitis (CH) and liver cirrhosis (LC). We have reported the possibility of GPC3-specific cytotoxic T lymphocytes (CTLs) serving as a marker for the early diagnosis of imaging invisible HCC. In this study, to identify new early diagnostic biomarker of imaging invisible HCC, we analyzed plasma of healthy donors and patients with CH, LC and HCC using surface-enhanced laser desorption-ionaization time-of-flight mass spectrometry (SELDI-TOF-MS). The intensities of four peaks were significantly increased in HCC patients compared with healthy donors. Two of these four peaks were significantly higher in CH and LC patients with GPC3-specific CTLs than in those without. One peak (11.7 kDa) was predicted to be beta2-microglobulin (beta2-MG) by molecular mass. There was a correlation between concentration of beta2-MG by latex agglutination immunoassay in plasma and peak intensity using SELDI-TOF-MS. The 11.7 kDa protein was fractionated by gel filtration and was identified as beta2-MG by Western blot analysis. These results suggest that the level of beta2-MG in plasma from patients with CH and LC could be a useful marker for the early diagnosis of imaging invisible HCC, however further investigation is needed.