Downregulation of Mus81 as a novel prognostic biomarker for patients with colorectal carcinoma

下调和上调 结直肠癌 肝细胞癌 癌症研究 转移 生物 肿瘤科 内科学 病理 医学 癌症 基因 遗传学
作者
Fan Wu,Atsushi Shirahata,Kazuma Sakuraba,Yohei Kitamura,Tetsuhiro Goto,Mariko Saito,Kazuyoshi Ishibashi,Gaku Kigawa,Hiroshi Nemoto,Yutaka Sanada,Kenji Hibi
出处
期刊:Cancer Science [Wiley]
卷期号:102 (2): 472-477 被引量:27
标识
DOI:10.1111/j.1349-7006.2010.01790.x
摘要

The Mus81 gene encodes a critical endonuclease involved in DNA repair and tumor suppression. Our previous study has shown reduced expression of Mus81 in hepatocellular carcinoma and its association with the metastatic potential and prognosis of hepatocellular carcinoma. However, the role of Mus81 in colorectal carcinoma is currently unknown. We therefore carried out the present study to explore the correlation between Mus81 expression and the progression of colorectal carcinoma. Mus81 expression in 92 cases of colorectal carcinoma and matched normal tissues was determined by quantitative real-time polymerase chain reaction. Our results showed that Mus81 expression in colorectal carcinoma tissues was significantly reduced compared with the corresponding normal tissues (P < 0.001) and the downregulation of Mus81 (decreased by more than 50%) was found in 60.9% (56/92) of colorectal carcinoma. Moreover, Mus81 downregulation correlated significantly to hepatic metastasis (P = 0.019) and a high TNM stage (P = 0.025) of colorectal carcinoma. In addition, the decrease of Mus81 was also detected in 10 cases of hepatic metastasis tissues compared with the corresponding primary colorectal carcinoma tissues (P = 0.016). More importantly, colorectal carcinoma patients with apparent Mus81 downregulation have shown significantly poorer overall survival than those with little Mus81 downregulation (P = 0.0374). Also, multivariable Cox regression analysis identified Mus81 downregulation as an independent prognostic factor for colorectal carcinoma (hazard ratio, 1.678; P = 0.040). In conclusion, the reduced expression of Mus81 is closely related to hepatic metastasis and poor prognosis of colorectal carcinoma, indicating Mus81 as a novel prognostic marker for colorectal carcinoma.

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