Xanthine oxidoreductase - Clinical significance in colorectal cancer and in vitro expression of the protein in human colon cancer cells
Xanthine oxidoreductase - Clinical significance in colorectal cancer and in vitro expression of the protein in human colon cancer cells
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DOI：
10.1016/j.ejca.2008.10.036
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发表时间：
2009-03-01
影响因子：
8.4
通讯作者：
Lundin, Johan
中科院分区：
文献类型：
--
作者：
Linder, Nina;Martelin, Eeva;Lundin, Johan
黄嘌呤氧化还原酶（XOR）是降解DNA和RNA的关键酶，以前已被证明在侵袭性乳腺癌和胃癌中降低。本研究评估了478例结直肠癌患者组织微阵列标本中XOR表达与临床参数的关系。此外，我们进行了体外研究XOR活性，蛋白质和mRNA在结肠癌细胞（Caco-2）。组织表达分析的结果显示，与正常组织相比，XOR在62%的肿瘤中降低，在22%的肿瘤中检测不到。异或丢失与分化程度差（p = 0.006）和晚期Dukes分期（p = 0.03）相关。在多变量生存分析中，XOR是一个预后因素（p = 0.008），独立于Dukes分期，组织学分级，年龄和肿瘤位置。体外分析表明，XOR在未分化的Caco-2细胞中不可测量，但随着分化而出现并增加。我们得出结论，XOR表达与结直肠癌的组织学分化程度和疾病程度相关，它提供了独立于既定因素的重要预后信息。(C)2008爱思唯尔有限公司保留所有权利。
Xanthine oxidoreductase (XOR) is a key enzyme in degradation of DNA and RNA, and has previously been shown to be decreased in aggressive breast and gastric cancer. In this study, XOR expression was assessed in tissue microarray specimens of 478 patients with colorectal cancer and related to clinical parameters. In addition, we performed in vitro studies of XOR activity, protein and mRNA in colon cancer cells (Caco-2). Results from the tissue expression analyses show that XOR was decreased in 62% and undetectable in 22% of the tumours as compared to normal tissue. Loss of XOR was associated with poor grade of differentiation (p = 0.006) and advanced Dukes stage (p = 0.03). In multivariate survival analysis, XOR was a prognostic factor (p = 0.008), independent of Dukes stage, histological grade, age and tumour location. The in vitro analyses show that XOR is not measurable in undifferentiated Caco-2 cells, but appears and increases with differentiation. We conclude that XOR expression is associated with histological grade of differentiation and extent of disease in colorectal cancer, and it provides significant prognostic information independently of established factors. (C) 2008 Elsevier Ltd. All rights reserved.