From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis.
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 the CK19-positive group had overt intrahepatic metastases (satellite nodules, p < 0.05; vascular tumor emboli, p < 0.001; tumor node metastatis staging, p < 0.001). CK19 fragment CYFRA 21-1 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.
Research Center for Proteome Analysis, Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS, Shanghai 200031, People's Republic of China.
Shi-Jian
SJ
Ding
Yan
Y
Li
Ye-Xiong
YX
Tan
Man-Rong
MR
Jiang
Bo
B
Tian
Ying-Kun
YK
Liu
Xiao-Xia
XX
Shao
Sheng-Long
SL
Ye
Jia-Rui
JR
Wu
Rong
R
Zeng
Hong-Yang
HY
Wang
Zhao-You
ZY
Tang
Qi-Chang
QC
Xia
D000818:Animals; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007633:Keratins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D011897:Random Allocation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D010446:Peptide Fragments; D020543:Proteome; D007633:Keratins