Linder Nina, Martelin Eeva, Lundin Mikael, Louhimo Johanna, Nordling Stig, Haglund Caj, Lundin Johan
Department of Oncology, Institute of Clinical Medicine, University of Helsinki, Haartmaninkatu 4, PO Box 105, 00029 Helsinki, Finland.
Eur J Cancer. 2009 Mar;45(4):648-55. doi: 10.1016/j.ejca.2008.10.036. Epub 2008 Dec 26.
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.
黄嘌呤氧化还原酶（XOR）是DNA和RNA降解中的关键酶，此前已发现在侵袭性乳腺癌和胃癌中其表达降低。在本研究中，对478例结直肠癌患者的组织微阵列标本进行了XOR表达评估，并将其与临床参数相关联。此外，我们对结肠癌细胞（Caco-2）进行了XOR活性、蛋白质和mRNA的体外研究。组织表达分析结果显示，与正常组织相比，62%的肿瘤中XOR表达降低，22%的肿瘤中未检测到XOR。XOR缺失与低分化程度（p=0.006）和晚期杜克分期（p=0.03）相关。在多因素生存分析中，XOR是一个预后因素（p=0.008），独立于杜克分期、组织学分级、年龄和肿瘤位置。体外分析表明，未分化的Caco-2细胞中无法检测到XOR，但随着细胞分化，XOR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范围相关，并且独立于已确定的因素提供重要的预后信息。
