Clinical significance of increased expression of Nijmegen breakage syndrome gene (NBS1) in human primary liver cancer.

Abstract

PURPOSE:

As a DNA repair-associated gene essential for maintaining genomic instability, Nijmegen breakage syndrome gene (NBS1), codes for a protein, Nbs1(p95/Nibrin), involved in the processing/repair of DNA double-strand breaks. The aim of this study is to investigate the molecular alteration of Nbs1 in human primary liver cancer, including HBV-associated hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

METHODS:

The expression levels of Nbs1 in 110 cases of primary liver cancer, including 85 HCCs and 25 ICCs, were detected by immunohistochemistry, real-time RT-PCR and Western blot analysis. The percentage of Ki-67 antigen-positive cells and the level of phosphorylated histone H2AX (γ-H2AX) were detected to evaluate the relationship of Nbs1 expression with proliferation and the degree of DNA damage in HCC cells.

RESULTS:

Increased Nbs1 expression was observed in tumor compared to corresponding adjacent non-tumor tissue in 54.6 and 47.3 % of HCC cases detected with frozen tissues and paraffin sections. Higher frequency of increased Nbs1 expression was shown in poorly differentiated HCCs (p = 0.0265) and in all poorly differentiated ICCs, indicating the increased Nbs1 expression is associated with the degree of malignancy of HCC cells. Moreover, the percentage of Ki-67-positive cells and the level of γ-H2AX correlate well with increased Nbs1 expression in HCC cases, suggesting an activated DNA damage response in proliferating HCC cells with increased Nbs1 expression.

CONCLUSION:

Increased Nbs1 expression might play a significant role in liver cancer progression, and the status of Nbs1 expression might be helpful for evaluation of the degree of malignancy of primary liver cancer.

• Authors: Yan Wang, Man Li, Jiang Long, Xiao-Yan Shi, Qian Li, Jia Chen, Wei-Min Tong, Ji-Dong Jia, Jian Huang
• Journal: Hepatology international (Hepatol Int) Vol. 8 Issue 2 Pg. 250-9 (Apr 2014) ISSN: 1936-0541 [Electronic] United States
• PMID: 26202506 (Publication Type: Journal Article)