Cytochrome P450 expression (CYP) in non-small cell lung cancer
Cytochrome P450 expression (CYP) in non-small cell lung cancer
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DOI：
10.2741/2232
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Yasumoto, Kosei
中科院分区：
文献类型：
--
作者：
Oyama, Tsunehiro;Sugio, Kenji;Yasumoto, Kosei
细胞色素P450（CYP 450）与肿瘤的发生和进展以及抗癌前药的活化及其代谢清除相关。本研究沿着78例非小细胞肺癌（NSCLC）患者的临床特征，探讨了芳香烃受体（AH-R）和4种CYP（CYP 1A 1、CYP 2A 6、CYP 2 E1和CYP 3A）的表达情况。在非小细胞肺癌中，这五种标记物主要在腺癌中表达，而在大多数鳞状细胞癌中不表达。在肺腺癌中，AH-R和CYP的表达均以女性为多，提示女性发生肺腺癌的危险性可能与AH-R和CYP的高表达有关。这些因子在早期腺癌和高分化腺癌中也更频繁表达。多种类型的CYP在早期腺癌中的表达比晚期腺癌更频繁。腺癌组织中AH-R、CYP 1A 1、CYP 2 E1和CYP 3A的表达呈正相关，提示在这些标志物的基因调控中存在代谢产物介导的串扰。但它们中的任何一个与CYP 2A 6的表达无关，提示CYP 2A 6在腺癌中的基因调控可能不同于其他三种CYP。CYP 1A 1和CYP 2 E1在肿瘤中的表达频率与其遗传多态性无关。晚期腺癌中表达一种以上CYP的患者的生存率低于不表达CYP的患者，提示晚期腺癌中CYP的表达可能与患者的生存率低有关。提示AH-R和4种CYP可能是判断肺癌性质的良好指标。这些信息将有助于通过分子靶向治疗更好地管理肺癌，并根据标记蛋白的个体谱选择抗癌药物。因此，肺癌组织中TNF-α蛋白的谱可能有助于改变目前的“订单”治疗为“定制”治疗。
The cytochrome P450 (CYP) is associated with tumor development and progression as well as activation of anti-cancer prodrugs and their metabolic clearance. In this study, we investigated the expression of aryl-hydrocarbon receptor (AH-R) and four CYPs (CYP1A1, CYP2A6, CYP2E1 and CYP3A) as putative diagnostic markers in 78 non-small cell lung cancers (NSCLC) along with clinical features of the patients. In non-small cell lung cancer, the expression of the five markers was mainly observed in adenocarcinoma but not in the most squamous cell cancers. The expression of them in adenocarcinoma was more frequent in females than in males, suggesting that a higher risk of women for developing lung adenocarcinoma might be associated with the frequent expression of AH-R and the CYPs. These factors were also more frequently expressed in early stage adenocarcinoma and more differentiated adenocarcinoma. Multiple types of CYPs are more frequently expressed in early stage of adenocarcinoma than in advanced stage of adenocarcinoma. There were positive relationships among AH-R, CYP1A1, CYP2E1 and CYP3A expressions in adenocarcinoma, which suggests a metabolite-mediated cross talk in the gene regulation of these markers. However, any of them was unrelated with the expression of CYP2A6, suggesting that the gene regulation of CYP2A6 in adenocarcinoma may be different from the other three CYPs. The expression frequency of CYP1A1 and CYP2E1 in tumors is independent of their genetic polymorphism. The survival of the patients with advanced adenocarcinoma expressing more than one of CYPs was lower rate than the patients with those expressing no CYPs, suggesting that the expression of the CYPs in advanced adenocarcinoma may be associated with poor survival. Our results suggest that AH-R and 4 CYPs may be good markers for the determination of quality of lung cancer. The information could be useful for the better management of lung cancer by molecular targeting therapy and selection of anticancer drug based on individual spectrum of the marker proteins. Therefore, the spectrum of CYP proteins in lung cancer could be useful for changing the present "order-made" therapy to the "tailor-made" therapy.