Plasma glutathione S-transferase P1-1 as a prognostic factor in patients with advanced non-Hodgkin's lymphoma (stages III and IV)
Plasma glutathione S-transferase P1-1 as a prognostic factor in patients with advanced non-Hodgkin's lymphoma (stages III and IV)
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DOI：
10.1158/1078-0432.ccr-03-0679
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发表时间：
2004-12-01
影响因子：
11.5
通讯作者：
Niitsu, Y
中科院分区：
文献类型：
--
作者：
Katahira, T;Takayama, T;Niitsu, Y
目的：本研究旨在探讨血浆谷胱甘肽s -转移酶P1-1 （GSTP1-1）水平是否可能是临床分期（CSs） III和iv期新生非霍奇金淋巴瘤（NHL）的预后因素，GSTP1-1是一种已知的抗癌药物耐药因子的II期解毒酶。实验设计：研究人群包括80例未接受治疗的NHL患者。12例患者处于CS I， 14例处于CS II， 25例处于CS III， 29例处于CS IV。所有54例处于CS III或CS IV的患者均接受环磷酰胺、阿霉素、长春新碱和强的松龙（CHOP）治疗。ELISA法测定血浆GSTP1-1浓度。我们使用抗GSTP1-1单克隆抗体5F对淋巴结组织进行GSTP1-1染色，并使用KS-400图像分析系统定量评估免疫染色强度。结果：血清GSTP1-1浓度从第1期到第4期逐渐升高（P < 0.05）。在54例接受CHOP治疗的CS III或IV患者中，28例（52%）血浆GSTP1-1水平升高。免疫染色结果显示，血浆GSTP1-1浓度与淋巴瘤组织中GSTP1-1表达强度呈正相关（P = 0.07）。GSTP1-1低、高血浆组CS III、CS IV患者的CR率分别为55.2%（26 / 14）、16.0%(28 / 5)，差异有统计学意义（P < 0.01）。两组患者的中位生存时间分别为64个月和25个月（P < 0.01），中位进展时间分别为58个月和12个月（P < 0.01）。单因素和多因素分析显示，这些患者血浆GSTP1-1浓度与其他NHL预后指标无显著相关性。结论：这些结果表明血浆GSTP1-1是CS III和IV期晚期NHL的有用预后因素。因此，与抗癌药物和gstp1 -1特异性抑制剂联合治疗NHL可能是一种很有前景的策略。
Purpose: This study aims to investigate whether the plasma level of glutathione S-transferase P1-1 (GSTP1-1), which is a phase II detoxifying enzyme known to be a resistance factor for anticancer drugs, could be a prognostic factor of de novo non-Hodgkin lymphoma (NHL) in clinical stages (CSs) III and IV.Experimental Design: Study population consisted of 80 NHL patients with no prior treatment: 12 patients were at CS I, 14 at CS II, 25 at CS III, and 29 at CS IV. All 54 patients at CS III or CS IV were treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Plasma GSTP1-1 concentration was measured by ELISA. We stained lymph node tissues for GSTP1-1 using anti-GSTP1-1 monoclonal antibody 5F and quantitatively assessed the intensity of immumostaining by using the KS-400 image analyzing system.Results: There was a significant stepwise increment of plasma GSTP1-1 concentration from CS I to CS IV (P < 0.05). Of the 54 patients with CS III or IV treated with CHOP, 28 (52%) had elevated plasma GSTP1-1 levels. Plasma GSTP1-1 concentration tended to correlate with the intensity of GSTP1-1 expression in lymphoma tissues as assessed by immunostaining (P = 0.07). The CR rates in patients at CS III and CS IV treated by CROP, 55.2% (14 of 26) and 16.0% (5 of 28) for the low and high plasma GSTP1-1 groups, respectively, were significantly different (P < 0.01). For these two groups, the median survival times were 64 and 25 months, respectively (P < 0.01), and the median times to progression were 58 and 12 months, respectively (P < 0.01). There was no significant correlation between plasma GSTP1-1 concentrations and other NHL prognostic indicators in these patients as determined by univariate and multivariate analyses.Conclusion: These results showed that plasma GSTP1-1 is a useful prognostic factor for CS III and IV advanced NHL. Thus, it may be a promising strategy to treat NHL concomitantly with anticancer drugs and GSTP1-1-specific inhibitors.