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Published on: February 10, 2015
Decreased expression of ING2 gene and its clinicopathological significance in hepatocellular carcinoma
Hua-kun Zhang1, Ke Pan, Hui Wang
1State 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.
Abstract:
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.
Insights
Inhibitor of growth 2 (ING2) is downregulated in hepatocellular carcinoma (HCC), correlating with tumor progression. Reduced ING2 expression indicates a poor prognosis for HCC patients, suggesting it acts as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Hepatology
Background:
- The Inhibitor of Growth 2 (ING2) protein regulates critical cellular processes like apoptosis and DNA repair.
- ING2's role in activating p53 and p53-mediated apoptosis suggests involvement in liver cancer development (hepatocarcinogenesis).
Purpose of the Study:
- To investigate the role of ING2 in hepatocellular carcinoma (HCC) pathogenesis.
- To analyze the correlation between ING2 expression levels and clinicopathologic factors in primary HCC.
- To determine the prognostic significance of ING2 in HCC.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot to assess ING2 transcription and protein levels.
- Immunohistochemistry to evaluate ING2 expression in HCC tissues.
- Kaplan-Meier survival analysis and multivariate analysis to assess prognostic value.
Main Results:
- ING2 expression was significantly downregulated at both transcriptional and post-transcriptional levels in HCC tumors compared to non-tumor liver tissues (p=0.004 and p=0.014).
- Reduced ING2 expression was observed in 52.4% of HCC cases and correlated with larger tumor size, specific histopathologic classifications, and elevated serum AFP levels.
- Lower ING2 expression was associated with significantly shorter survival times (p=0.009) and identified as an independent prognostic factor.
Conclusions:
- ING2 plays a role in HCC progression and is a potential tumor suppressor gene.
- Significantly decreased ING2 expression in HCC is linked to an unfavorable prognosis.
- ING2 may serve as a valuable biomarker for predicting HCC patient outcomes.
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