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获得性黄嘌呤脱氢酶表达缩短了肺切除腺癌患者的生存期。

Acquired xanthine dehydrogenase expression shortens survival in patients with resected adenocarcinoma of lung.

作者信息

Konno Hayato, Minamiya Yoshihiro, Saito Hajime, Imai Kazuhiro, Kawaharada Yasushi, Motoyama Satoru, Ogawa Jun-ichi

机构信息

Division of Chest Surgery, Akita University Hospital, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita City, 010-8543, Japan.

出版信息

Tumour Biol. 2012 Oct;33(5):1727-32. doi: 10.1007/s13277-012-0431-2. Epub 2012 Jun 8.

DOI:10.1007/s13277-012-0431-2
PMID:22678977
Abstract

Xanthine dehydrogenase (XDH), also known as xanthine oxidoreductase (XOR), has long been recognized as the key enzyme in the catabolism of purines, oxidizing hypoxanthine into xanthine and then xanthine into uric acid. In addition, levels of XDH expression are reportedly related to the prognosis of patients with malignant tumors, though the relationship between the clinicopathological features of lung cancer and XDH is not fully understood. We therefore used semiquantitative real-time reverse transcription polymerase chain reaction to assess expression of XDH mRNA in tumor samples from 88 patients with adenocarcinoma of the lung. We then correlated XDH mRNA levels with known clinicopathological factors. We found that the 5-year overall survival rate among patients strongly expressing XDH was significantly poorer than among those expressing lower levels of XDH (P < 0.001; log-rank test). Normal lung tissue does not express XDH. Multivariate Cox proportional hazard analyses revealed that being male (hazard ratio, 3.14; 95 % confidence interval (CI), 1.45-7.07; P = 0.004), nodal metastasis positivity (hazard ratio, 5.74; 95 % CI, 1.94-19.3; P = 0.001), and high XDH expression (hazard ratio, 2.33; 95 % CI, 1.11-5.02; P = 0.026) were all independent factors affecting 5-year disease-free survival. In conclusion, high tumoral XDH expression is an independent predictor of a poor prognosis in patients with adenocarcinoma of the lung.

摘要

黄嘌呤脱氢酶(XDH),也被称为黄嘌呤氧化还原酶(XOR),长期以来一直被认为是嘌呤分解代谢中的关键酶,它将次黄嘌呤氧化为黄嘌呤,然后再将黄嘌呤氧化为尿酸。此外,据报道XDH的表达水平与恶性肿瘤患者的预后相关,尽管肺癌的临床病理特征与XDH之间的关系尚未完全明确。因此,我们使用半定量实时逆转录聚合酶链反应来评估88例肺腺癌患者肿瘤样本中XDH mRNA的表达情况。然后,我们将XDH mRNA水平与已知的临床病理因素进行关联分析。我们发现,XDH高表达患者的5年总生存率显著低于XDH低表达患者(P<0.001;对数秩检验)。正常肺组织不表达XDH。多因素Cox比例风险分析显示,男性(风险比,3.14;95%置信区间(CI),1.45 - 7.07;P = 0.004)、淋巴结转移阳性(风险比,5.74;95%CI,1.94 - 19.3;P = 0.001)和XDH高表达(风险比,2.33;95%CI,1.11 - 5.02;P = 0.026)均为影响5年无病生存的独立因素。总之,肿瘤XDH高表达是肺腺癌患者预后不良的独立预测因素。

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Int J Clin Oncol. 2012 Jun;17(3):250-5. doi: 10.1007/s10147-011-0283-6. Epub 2011 Jul 13.
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Tumor invasion induced by oxidative stress is dependent on membrane ADAM 9 protein and its secreted form.
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