Involvement of RhoA in progression of human hepatocellular carcinoma.
OBJECTIVE
The activation of Rho proteins has been shown to lead to loss of polarity in cancer cells, as well as reorganization of the cytoskeleton and facilitation of cell motility, possibly resulting in their malignant potential. The clinicopathological significance of RhoA, however, is not yet well known in the case of hepatocellular carcinoma (HCC). This study evaluated the clinicopathological correlation of RhoA levels with HCC.


METHODS
The intratumor expression level of Rho was determined and compared with that in adjacent non-cancerous hepatic tissue using quantitative real time RT-PCR and Western blotting in 64 patients with HCC. Relationships between the level of RhoA and clinicopathological factors were examined. RhoA protein expression was confirmed by immunohistochemistry.


RESULTS
RhoA immunostaining was strong in malignant tissue whereas it was minimal in benign tissue. Tumor tissue of HCC patients demonstrated a copy number of RhoA mRNA that was well correlated with its protein level in each case and was significantly higher than that found in the corresponding non-cancerous liver tissue (P < 0.01). With regard to venous invasion, satellite lesions and advanced pTNM stage, the RhoA level tended to be higher in HCC than that seen in negative tissue (P < 0.05).


CONCLUSIONS
This is the first demonstration that the expression level of RhoA is correlated with tumor progression and metastasis in HCC. RhoA in tumor tissue might be expected to be not only a good candidate marker for invasive and proliferative tumor cells, but also a molecular target of these cells.
Wang
Desheng
D
Department of Hepatobiliary Surgery, Xijing Hospital, Xi'an, Shannxi Province, China.
Dou
Kefeng
K
Xiang
Hongjun
H
Song
Zhenshun
Z
Zhao
Qingchuan
Q
Chen
Yong
Y
Li
Yu
Y
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D020742:rhoA GTP-Binding Protein / Q000032:analysis* / Q000235:genetics
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein