Glutathione-associated enzymes in head and neck squamous cell carcinoma and response to cisplatin-based neoadjuvant chemotherapy
Glutathione-associated enzymes in head and neck squamous cell carcinoma and response to cisplatin-based neoadjuvant chemotherapy
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DOI：
10.1002/ijc.1392
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发表时间：
2001-09-01
影响因子：
6.4
通讯作者：
De Waziers, I
中科院分区：
文献类型：
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作者：
Cabelguenne, A;Loriot, MA;De Waziers, I
谷胱甘肽S-转移酶（GST）是代谢第二阶段酶，通过将其与谷胱甘肽（GSH）结合来促进反应性代谢物的消除。由于它们在异生物质代谢和解毒中的重要作用，它们已被牵连到致癌过程，特别是上皮转化。此外，它们对癌症患者化疗反应的影响已得到证实。GSTM 1、GSTT 1 ′和GSTP 1的遗传多态性已在人群中发现，并已显示具有表型后果。为了研究GST酶在头颈部鳞状细胞癌（HNSCC）患者的癌变和对化疗的反应中的作用，在大量的HNSCC患者中前瞻性地研究了GST P1、GST M1和GST T1。研究GST改变、p53突变状态与化疗临床反应之间的相关性。我们发现GSTM 1无效基因型患者发生喉癌的风险增加2.6倍[95%CI 1.6-6.1]，GSTP 1 val 105纯合基因型患者发生喉癌的风险增加2.8倍[95%CI 0.9-8.1]。此外，具有后一种基因型的个体在p53突变组中的代表性过高（p = 0.05）。储存时间和溶血调整后，完全应答者血浆GST 1水平显著低于部分应答者和无应答者（平均值分别为：4.4 +/- 0.06 mug/l、4.7 +/- 0.06 mug/l和4.7 +/- 0.07 mug/l; p = 0.05）。p53突变肿瘤的患病率在无应答组（81%）中显著高于部分应答组（60%）和完全应答组（64%）（p = 0.05）。进行了两种类型的多变量分析，包括在单变量分析中已显示出显著影响化疗反应的参数。p53突变和肿瘤分期高是化疗无应答的独立因素，而血浆GSTP 1水平和肿瘤分期低是化疗完全应答的独立因素。我们的数据表明，GST酶与喉癌有关，其作为预测因子和治疗靶点的应用应进一步探讨。(C)2001 Wiley-Liss，Inc.
Glutathione S-transferases (GSTs) are metabolic phase II enzymes that promote reactive metabolite elimination by conjugating them to glutathione (GSH). Because of their important role in xenobiotic metabolism and detoxification, they have been implicated in carcinogenesis processes, especially epithelium transformation. Moreover, their influence on response to chemotherapy in cancer patients has been demonstrated. Genetic polymorphisms for GSTM1, GSTT1' and GSTP1 have been found in human populations and have been shown to have phenotypic consequences. To investigate the role of GST enzymes in carcinogenesis and in response to chemotherapy in patients with head and neck squamous cell carcinoma (HNSCC), GSTP1, GSTM1 and GSTT1 were studied prospectively in a large series of HNSCC patients. Correlations between GST alterations, p53 mutation status and clinical response to chemotherapy were investigated. We showed that the risk of developing laryngeal cancer was increased by 2.6-fold [9S% Cl 1.6-6.1] in patients with the GSTM1 null genotype and by 2.8-fold [95% CI 0.9-8.1] in patients with the homozygous GSTP1 val105 genotype. Furthermore, individuals with this latter genotype were overrepresented in the p53 mutation group (p = 0.05). After storage duration and hemolysis adjustement, a significantly lower plasmatic GSTP1 level was observed in complete responders compared with partial and non-responders (mean: 4.4 +/- 0.06 mug/l, 4.7 +/- 0.06 mug/l and 4.7 +/- 0.07 mug/l; p = 0.05), respectively. The prevalence of p53-mutated tumors was significantly higher in the group of non-responders (81%) compared with partial (60%) and complete responders (64%) (p = 0.05). Two types of multivariate analysis were performed including parameters that have been shown to influence response to chemotherapy significantly in univariate analysis. p53 mutations and high tumor stage are independent factors of non-response to chemotherapy, whereas plasmatic GSTP1 levels and low tumor stage are independent factors of complete response. Our data suggest that GST enzymes are associated with larynx cancer and that their use as predictive factors and treatment targets should be further explored. (C) 2001 Wiley-Liss, Inc.