Prognostic relevance of melanoma antigen D1 expression in colorectal carcinoma
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RESEARCH
Open Access
Prognostic relevance of melanoma antigen D1 expression in colorectal carcinoma Zhao-lei Zeng1,2†, Wen-jing Wu1,3, Jing Yang1,2, Zhen-jie Tang1,2, Dong-liang Chen1,3, Miao-zhen Qiu1,3, Hui-yan Luo1,3, Zhi-qiang Wang1,3, Ying Jin1,3, De-shen Wang1,3 and Rui-hua Xu1,3*
Abstract Background: Melanoma antigen D1 (MAGED1) is a member of the type II melanoma antigen (MAGE) family. The down-regulation of MAGED1 expression has been shown in breast carcinoma cell lines and in glioma stem cells and may play an important role in apoptosis and anti-tumorigenesis. However, there is no report on its clinical role in colorectal cancer (CRC). Methods: We examined the expression of MAGED1 by qPCR in colorectal cancer tissues and their adjacent nontumorous tissues taken from 6 cases and performed Western blotting and IHC analyses. In addition, we analyzed MAGED1 expression in 285 clinicopathologically characterized colorectal cancer patients. Results: MAGED1 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues and was associated with clinical stage (p < 0.001), T classification (p = 0.001), N classification (p < 0.001), M classification (p < 0.001) and pathologic differentiation (p = 0.002). Patients with lower MAGED1 expression had a shorter survival time than those with higher MAGED1 expression. Univariate and multivariate analyses indicated that MAGED1 expression was an independent prognostic factors (p < 0.001). Conclusions: MAGED1 may serve as a novel prognostic biomarker of human colorectal cancer. Keywords: MAGED1, Colorectal cancer, Melanoma antigen and prognosis
Background The melanoma antigen (MAGE) family, which includes more than 25 members, is classified into two subfamilies based on the structural differences of the genes and tissuespecific gene expressions. Type I MAGE genes are classically subdivided into three clusters (MAGE-A, B, and C), which are expressed in a variety of cancer cells, but are seldom expressed in normal cells [1-4]. Type II MAGE genes include MAGE-D (MAGED1 to MAGED14), MAGEE1 to H1, MAGEL2 and NECDIN [5]. In contrast to type I MAGE genes, type II MAGE genes are expressed in a variety of normal tissues and cell lines [6,7]. Melanoma antigen D1 (MAGED1), also known as Dlxin-1 or NRAGE, is a member of the type II MAGE * Correspondence: [email protected] † Equal contributors 1 State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China 3 Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China Full list of author information is available at the end of the article
family. It was reported that MAGED1 modulated the transcriptional activity of DLx5/Msx2, regulating osteoblast differentiation during development [8,9]. Unlike the type I MAGE genes, which encode tumor antigens, MAGED1 encodes a protein involved in the apoptosis pathway. MAGED1 mediates cellular apoptosis and cell cycle arrest through the c-JNK and p53-dependent pathways [10-12], and is also involved i
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