Proteomic analysis of hepatitis B virus-associated hepatocellular carcinoma: Identification of potential tumor markers.
Hepatocellular carcinoma (HCC) is a malignancy of both underdeveloped and developing countries. Proteomes of ten pairs of clinical hepatitis B virus associated HCC tissue samples were obtained by high resolution two-dimensional gel electrophoresis. Comprehensive analyses of proteins associated with B-type HCC were focused on total differentially expressed proteins (> or = two-fold increase or decrease, Student's t-test, p < 0.05) from one pair of samples. Protein identification was done by peptide mass fingerprinting with matrix assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry. Comparative analyses of proteins associated with B-type HCC included repeat statistics in ten cases. A total of 100 protein spots, corresponding to 80 different gene products, were identified. Proteins whose expression levels were different by more than 2-fold in at least 50% of the cases (five of ten cases) were further analyzed and 45 proteins were selected out as candidates for HCC-associated proteins. Western blotting further validated up-regulated expressions of two candidate proteins in tumor tissues: proliferating cell antigen and stathmin 1. This comprehensive and comparative analyses of proteins associated with B-type HCC could provide useful molecular markers for diagnostics and prognostics and for therapeutic targets. The physiological significance of the differential expressions for several candidate proteins are discussed.
Li
Chen
C
Research Center for Proteome Analysis, Key Lab of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Tan
Ye-Xiong
YX
Zhou
Hu
H
Ding
Shi-Jian
SJ
Li
Su-Jun
SJ
Ma
Dan-Jun
DJ
Man
Xiao-Bo
XB
Hong
Yi
Y
Zhang
Lei
L
Li
Long
L
Xia
Qi-Chang
QC
Wu
Jia-Rui
JR
Wang
Hong-Yang
HY
Zeng
Rong
R
D000328:Adult; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000821:virology*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D019295:Computational Biology / Q000379:methods*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008868:Microtubule Proteins / Q000096:biosynthesis; D008875:Middle Aged; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D020033:Protein Isoforms; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D050777:Stathmin; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D008868:Microtubule Proteins; D010750:Phosphoproteins; D018809:Proliferating Cell Nuclear Antigen; D020033:Protein Isoforms; C493995:STMN1 protein, human; D050777:Stathmin