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Submitted on September 11, 2003
Research Center for Proteome Analysis, Institute of Biochemistry and Cell Biology, Shanghai, Shanghai 200031
Corresponding Author: dsj{at}sunm.shcnc.ac.cn
To better understand the mechanism underlying the hepatocellular carcinoma (HCC) metastasis and to search potential markers for HCC prognosis, differential proteomic analysis on two well established HCC cell strains with high and low metastatic potentials, MHCC97-H and MHCC97-L, was conducted using two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/time of flight mass spectrometry. Cytokeratin 19 (CK19) was identified and found to be overexpressed in MHCC97-H as compared with MHCC97-L. This result was further confirmed by two-dimensional Western Blot analysis and immunofluorescence assay. Furthermore, one-dimensional Western Blot analysis showed consistently increased CK19 expression in progressively more metastatic cells. Immunohistochemical study on 102 human HCC specimens revealed that more patients in CK19 positive group had overt intrahepatic metastases (satellite nodules, P<0.05; vascular tumor emboli, P<0.001; tumor TNM staging, P<0.001). CK19 fragment CYFRA21-1 levels measured in sera from nude mice model of human HCC metastasis with radioimmunoassay increased in parallel with tumor progression and rose remarkably when pulmonary metastases occurred. The results demonstrated that overexpression of CK19 in HCC cells is related to metastatic behavior. Serum CK19 level might reflect the pathological progression in some HCC and may be a useful marker for predicting tumor metastasis and a therapeutic target for the treatment of HCC patients with metastases.
Revised on October 26, 2003
Accepted on October 30, 2003
From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis
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