Decreased expression of ING2 gene and its clinicopathological significance in hepatocellular carcinoma.
The inhibitor of growth (ING) family member 2 (ING2) is a newly discovered member of ING family that can regulate a wide range of cellular processes including cell growth arrest, apoptosis, and DNA repair. Researches have shown that ING2 can activate p53 and p53-mediated apoptotic pathway involved in the hepatocarcinogenesis. To investigate the role of ING2 in hepatocellular carcinoma (HCC) pathogenesis, we analyzed the correlations between the ING2 expression level and clinicopathologic factors and studied its prognostic role in primary HCC. Using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, ING2 transcription and post-transcription level was found to be downregulated in the majority of tumors compared with matched non-tumors liver tissues (p=0.004 and p=0.014, respectively). The immunohistochemistry data indicated significant reduction of ING2 expression level in 44 of 84 (52.4%) HCC cases. In addition, the expression level of ING2 correlated with tumor size, histopathologic classification, serum AFP (p<0.05). Kaplan-Meier curves demonstrated that patients with reduced ING2 expression were at significantly increased risk for shortened survival time (p=0.009). Using multivariate analysis, ING2 expression was found to be an independent prognostic factor. Our data suggest that ING2 is involved in the progression of HCC, therefore it is considered to be a candidate tumor suppressor gene and its significantly decreased expression in HCC may lead to an unfavorable prognosis.
Zhang
Hua-kun
HK
State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Yuexiu District, Guangzhou, Guangdong Province 510060, PR China.
Pan
Ke
K
Wang
Hui
H
Weng
De-sheng
DS
Song
Hai-feng
HF
Zhou
Jun
J
Huang
Wei
W
Li
Jian-jun
JJ
Chen
Min-shan
MS
Xia
Jian-chuan
JC
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018398:Homeodomain Proteins; C444654:ING2 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D025521:Tumor Suppressor Proteins