Overexpressed Id-1 is associated with a high risk of hepatocellular carcinoma development in patients with cirrhosis without transcriptional repression of p16.
BACKGROUND
Inhibitor of differentiation/DNA binding protein 1 (Id-1) plays a pivotal role in the regulation of cell proliferation and carcinogenesis via inhibiting basic helix-loop-helix (HLH) transcription factors. Recently, Id-1 was found to repress p16 in tumorous tissue specimens including hepatocellular carcinoma (HCC), but its relevance in precancerous liver tissues is unknown.


METHODS
Id-1 expression in the liver tissue specimens of 112 patients with cirrhosis without HCC was studied by immunohistochemical analysis. Correlations were investigated between Id-1 expression and clinicopathologic features, the status of p16, and the risk of HCC occurrence.


RESULTS
A high expression of Id-1 was observed in 42 patients (38%). The level of Id-1 expression was not associated with clinical standard parameters or the status of p16 in cirrhotic tissue specimens. The cumulative incidence of HCC development was significantly higher in a group of patients with high Id-1 expression (P = 0.0008). Multivariate analysis revealed that increased Id-1 expression is an independent significant factor for the risk of HCC development in patients with cirrhosis (relative risk = 2.75, P = 0.003).


CONCLUSIONS
The results of the current study suggested that increased expression of Id-1 may play an important role in the early step of hepatocarcinogenesis, and might serve as a useful marker for determining patients with cirrhosis with a high risk of HCC occurrence.
Matsuda
Yasunobu
Y
Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan. yasunobu@med.niigata-u.ac.jp
Yamagiwa
Satoshi
S
Takamura
Masaaki
M
Honda
Yutaka
Y
Ishimoto
Yuiko
Y
Ichida
Takafumi
T
Aoyagi
Yutaka
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000032:analysis* / Q000502:physiology; D012306:Risk; D014157:Transcription Factors / Q000032:analysis* / Q000502:physiology
D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors