Smad4 expression in hepatocellular carcinoma differs by hepatitis status.
OBJECTIVE
Primary hepatocellular carcinoma (HCC) is a common malignancy often related to hepatitis viral infection. Smad4 is known to mediate the TGF-β pathway to suppress tumorigenesis. However, the function of Smad4 in HCC is still controversial. In this study we compared levels of Smad4 in HCC tissues with or without hepatitis virus infection and adjacent normal-appearing liver.


METHODS
Samples from HCC patients were analyzed for Smad4 protein and mRNA expression by immunohistochemistry (IHC), RT-PCR and Western blotting.


RESULTS
We found that tumor tissues expressed less Smad4 mRNA and protein than the adjacent tissues. Most HCC tumor tissues were negative for Smad4 in IHC staining, while the majority of adjacent tissues were positively stained. Interestingly, protein levels were higher in HCC tissues with viral hepatitis than those without virus infection. Suppression of expression appeared closely related to HCC, so that Smad4 appears to function as a tumor suppressor gene (TSG).


CONCLUSIONS
Patients with hepatitis viral infection, at higher risk for HCC, exhibited increased Smad4 protein expression suggesting hepatitis virus may modulate Smad4 expression, which is functionally distinct from its putative role as a TSG. Smad4 expression may thus be an applicable marker for diagnosis and/or a target to develop therapeutic agents for HCC.
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Lei
L
Yao
Fu-Jun
FJ
Li
Zhi-Qiang
ZQ
Tang
Shuang
S
Gao
Qe-Quan
QQ
Wu
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism*; D018709:Statistics, Nonparametric; D015996:Survival Rate
D012333:RNA, Messenger; C497796:SMAD4 protein, human; D051901:Smad4 Protein