Significance of NQO1 overexpression for prognostic evaluation of gastric adenocarcinoma
Significance of NQO1 overexpression for prognostic evaluation of gastric adenocarcinoma
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NQO1过表达对胃腺癌预后评估的意义
DOI：
10.1016/j.yexmp.2013.12.008
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发表时间：
2014-04-01
影响因子：
3.6
通讯作者：
Lin, Zhenhua
中科院分区：
文献类型：
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作者：
Lin, Lijuan;Qin, Yunzhi;Lin, Zhenhua
NQO1（NAD(P)H：醌氧化还原酶，也称为DT - 黄递酶）在维持细胞内稳态中起重要作用。NQO1在许多实体癌类型中异常升高，包括肾上腺、乳腺、结肠、肺、卵巢和甲状腺的癌症。然而，对于NQO1在胃腺癌（GAC）中的情况知之甚少。为了研究NQO1在GAC中表达的临床病理意义，从而评估其作为潜在预后标志物的作用，选取203例原发性GAC、31例胃异型增生和53例邻近非肿瘤组织进行NQO1蛋白的免疫组化染色。通过卡方检验和费舍尔精确检验评估NQO1过表达与临床病理特征之间的相关性，同时通过卡普兰 - 迈耶方法计算生存率。通过考克斯比例风险模型分析预后因素与患者生存之间的关系。通过这些分析发现，GAC中NQO1蛋白的强阳性率显著高于胃异型增生和邻近非肿瘤组织。实时定量聚合酶链反应（qRT - PCR）分析也证实，与在邻近非肿瘤组织或正常胃黏膜中检测到的相比，GAC中NQO1 mRNA水平升高。此外，NQO1表达率与肿瘤大小、浆膜侵犯、肿瘤分期以及无病生存率和5年生存率呈正相关。进一步分析表明，尽管NQO1不是GAC的独立预测因子，但NQO1表达升高可预测晚期患者较低的无病生存率和5年生存时间。总之，NQO1在GAC的进展中起重要作用，并且可能是GAC的一个潜在的、但不是独立的不良预后生物标志物和治疗靶点。（C）2013爱思唯尔公司。保留所有权利。
NQO1 (NAD(P)H: quinone oxidoreductase, also known as DT-diaphorase) plays a prominent role in maintaining cellular homeostasis. NQO1 is abnormally elevated in many solid cancer types, including those of the adrenal gland, breast, colon, lung, ovary, and thyroid. However, little is known about the status of NQO1 in gastric adenocarcinoma (GAC). To investigate the clinicopathological significance of NQO1 expression in GAC, and thus evaluate its role as a potential prognostic marker, 203 cases of primary GAC, 31 of gastric dysplasia, and 53 of adjacent non-tumor tissues were selected for immunohistochemical staining of NQO1 protein. Correlations between NQO1 overexpression and clinicopathological characteristics were evaluated by 2,2 test and Fisher's exact test, while survival rates were calculated by Kaplan-Meier method. The relationship between prognostic factors and patient survival was analyzed by Cox proportional hazards model.Through these analyses it was found that the strongly positive rate of NQO1 protein in GAC was significantly higher than that in gastric dysplasia and adjacent non-tumor tissues. Analysis by qRT-PCR also confirmed that NQO1 mRNA levels were increased in GAC compared with those detected in either adjacent non-tumor tissues or normal gastric mucosa. Additionally, the NQO1 expression rate was positively correlated with tumor size, serosal invasion, tumor stage, and both disease-free survival and 5-year survival rates. Further analysis showed that although NQO1 was not an independent predictor of GAC, elevated expression of NQO1 could predict lower disease-free survival and 5-year survival times in late-stage patients. In conclusion, NQO1 plays an important role in the progression of GAC, and might be a potential, but not an independent, poor prognostic biomarker and therapeutic target of GAC. (C) 2013 Elsevier Inc. All rights reserved.