title: Downregulation of Mus81 as a novel prognostic biomarker for patients with colorectal carcinoma.
abstract: 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.
authors.affiliation: Department of General Surgery, Guangzhou Red Cross Hospital Fourth Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shirahata
authors.forename: Kazuma
authors.initials: K
authors.lastname: Sakuraba
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Goto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Saito
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Gaku
authors.initials: G
authors.lastname: Kigawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nemoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sanada
authors.forename: Kenji
authors.initials: K
authors.lastname: Hibi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015536:Down-Regulation; D004720:Endonucleases / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004720:Endonucleases; C498772:MUS81 protein, human