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Int J Biol Sci 2012; 8(8):1168-1177. doi:10.7150/ijbs.4778

Research Paper

High Level of COP1 Expression is Associated with Poor Prognosis in Primary Gastric Cancer

Yuan-fang Li1,2#, Dan-dan Wang1#, Bai-wei Zhao1,2#, Wei Wang1,2, Chun-yu Huang1,2, Yong-ming Chen1,2, Yan Zheng1,2, Rajiv Prasad Keshari1,2, Jian-chuan Xia1✉, Zhi-wei Zhou1,2✉

1. State Key Laboratory of Oncology in South China and Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China;
2. Department of Gastric and Pancreatic Surgery, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
# These authors contributed equally to this work.

Abstract

COP1 (constitutive photomorphogenic 1, also known as RFWD2) is a p53-targeting E3 ubiquitin ligase containing RING-finger, coiled-coil, and WD40-repeat domains. Recent studies have identified that COP1 is overexpressed in several cancer types and that increased COP1 expression promotes cell proliferation, cell transformation, and tumor progression. In the present study, we investigated the expression and prognostic value of COP1 in primary gastric cancer. To investigate the role of the COP1 gene in primary gastric cancer pathogenesis, real-time quantitative PCR and western blotting were performed to examine COP1 expression in paired cancerous and matched adjacent noncancerous gastric tissues. The results revealed high COP1 mRNA (P=0.030) and protein (P=0.008) expression in most tumor-bearing tissues compared with the matched adjacent non-tumor tissues. The correlated protein expression analysis revealed a negative correlation between COP1 and p53 in gastric cancer samples (P=0.005, r=-0.572). Immunohistochemical staining of gastric cancer tissues from the same patient showed a high COP1 expression and a low p53 expression. To further investigate the clinicopathological and prognostic roles of COP1 expression, we performed immunohistochemical analysis of 401 paraffin-embedded gastric cancer tissue blocks. The data revealed that high COP1 expression was significantly correlated with T stage (P=0.030), M stage (P=0.048) and TNM stage (P=0.022). Consistent with these results, we found that high expression of COP1 was significantly correlated with poor survival in gastric cancer patients (P<0.001). Cox regression analyses showed that COP1 expression was an independent predictor of overall survival (P<0.001). Our data suggest that COP1 could play an important role in gastric cancer and might serve as a valuable prognostic marker and potential target for gene therapy in the treatment of gastric cancer.

Keywords: COP1, gastric cancer, expression, immunohistochemistry, prognosis.

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How to cite this article:
Li Yf, Wang Dd, Zhao Bw, Wang W, Huang Cy, Chen Ym, Zheng Y, Keshari RP, Xia Jc, Zhou Zw. High Level of COP1 Expression is Associated with Poor Prognosis in Primary Gastric Cancer. Int J Biol Sci 2012; 8(8):1168-1177. doi:10.7150/ijbs.4778. Available from http://www.ijbs.com/v08p1168.htm