[Serum proteomic analysis on metastasis-associated proteins of hepatocellular carcinoma].
OBJECTIVE
To screen the serum proteins associated with the metastasis of hepatocellular carcinoma (HCC) using a comparative proteomic approach.


METHODS
The serum samples of HCC patients with the same disease background were divided into metastatic (n=20) and non-metastatic (n=20) groups. The proteins extracted from the patients and 20 normal subjects, after depletion of the highly abundant proteins, underwent two-dimensional gel electrophoresis (2-DE). Comparative analyses of the 2-DE protein patterns between the 3 groups were conducted using a computerized image analysis system. The proteins with statistically significant differential expression between the metastatic and non-metastatic patients were identified by mass spectrometry. Western blotting was performed to examine the differential expression of the candidate proteins.


RESULTS
Four protein spots were identified by mass spectrometry among the 12 differentially expressed protein spots in the serum samples of HCC patients with intrahepatic metastasis, and confirmed by searching in MASCOT database. Of the 4 proteins, cytokeratin 9 (CK9) was up-regulated by 2 folds, and inter-alpha (globulin) inhibitor H4, complement factor H-related protein 1 precursor (FHR-1), and apolipoprotein E were down-regulated by 2 folds. CK9 was found to be specifically over-expressed in the metastatic group in comparison with the non-metastatic group, as confirmed by Western blotting.


CONCLUSIONS
The metastasis of HCC might be correlated to the specific variation of protein expression profiles. The overexpression of CK9 may play a crucial role in HCC metastasis, and can be used as a potential serum marker for predicting HCC metastasis.
Fu
Bin-sheng
BS
Organ Transplantation Center, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou. andyfu79@163.com
Liu
Wei
W
Zhang
Jian-wen
JW
Zhang
Tong
T
Li
Hua
H
Chen
Gui-hua
GH
D000328:Adult; D001798:Blood Proteins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000097:blood / Q000235:genetics; D006801:Humans; D053534:Keratin-9 / Q000097:blood* / Q000235:genetics; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D053491:Proteinase Inhibitory Proteins, Secretory / Q000097:blood / Q000235:genetics; D040901:Proteomics; D015854:Up-Regulation
D001798:Blood Proteins; D006023:Glycoproteins; C091236:ITIH4 protein, human; D053534:Keratin-9; D053491:Proteinase Inhibitory Proteins, Secretory