生殖细胞肿瘤患者谷胱甘肽 S 转移酶 M1 表达与治疗效果之间的关系

IF 2 4区 医学 Q3 ONCOLOGY
Michal Mego, Katarina Kalavska, Samuel Horak, Michaela Hyblova, Georgina Kolnikova, Vera Novotna, Kristina Majtanova, Gabriel Minarik, Lucia Kucerova, Zuzana Cierna
{"title":"生殖细胞肿瘤患者谷胱甘肽 S 转移酶 M1 表达与治疗效果之间的关系","authors":"Michal Mego, Katarina Kalavska, Samuel Horak, Michaela Hyblova, Georgina Kolnikova, Vera Novotna, Kristina Majtanova, Gabriel Minarik, Lucia Kucerova, Zuzana Cierna","doi":"10.4149/neo_2024_240609N249","DOIUrl":null,"url":null,"abstract":"<p><p>Cisplatin-based chemotherapy is the mainstay in the treatment of germ cell tumors (GCTs). Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by chemotherapy and are thus implicated in developing treatment resistance. This study aimed to assess the expression level of GST mu 1 (GSTM1) and its association with treatment outcomes in patients with GCT. This translational study included tumor specimens from 207 patients with newly diagnosed GCTs, as well as cisplatin-sensitive GCT cell line xenografts and their resistant variants for all histological variants of GCTs. GSTM1 expression was detected by reverse transcription-quantitative PCR and immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method. GSTM1 expression was correlated with patient/tumor characteristics and treatment outcomes. The highest GSTM1 expression was observed in seminoma, followed by choriocarcinoma, embryonal carcinoma, and yolk sac tumor, while the lowest was observed in teratoma (p<0.0001). There was no association between GSTM1 expression in tumor tissue and patient/tumor characteristics. The low GSTM1 expression was associated with significantly better relapse-free survival compared with high GSTM1 (HR=0.50, 95% CI 0.23-1.09, p=0.03) but not overall survival (HR=0.61, 95% CI 0.24-1.54, p=0.22). Multivariate analysis showed that the prognostic value of GSTM1 was independent of the International Germ Cell Cancer Collaborative Group (IGCCCG) score. These data revealed the prognostic value of GSTM1 in GCTs, with a high GSTM1 expression associated with worse outcomes, suggesting that GSTM1 could be responsible, in part, for treatment resistance in GCTs.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 4","pages":"374-386"},"PeriodicalIF":2.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association between glutathione S-transferases M1 expression and treatment outcome in germ cell tumor patients.\",\"authors\":\"Michal Mego, Katarina Kalavska, Samuel Horak, Michaela Hyblova, Georgina Kolnikova, Vera Novotna, Kristina Majtanova, Gabriel Minarik, Lucia Kucerova, Zuzana Cierna\",\"doi\":\"10.4149/neo_2024_240609N249\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cisplatin-based chemotherapy is the mainstay in the treatment of germ cell tumors (GCTs). Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by chemotherapy and are thus implicated in developing treatment resistance. This study aimed to assess the expression level of GST mu 1 (GSTM1) and its association with treatment outcomes in patients with GCT. This translational study included tumor specimens from 207 patients with newly diagnosed GCTs, as well as cisplatin-sensitive GCT cell line xenografts and their resistant variants for all histological variants of GCTs. GSTM1 expression was detected by reverse transcription-quantitative PCR and immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method. GSTM1 expression was correlated with patient/tumor characteristics and treatment outcomes. The highest GSTM1 expression was observed in seminoma, followed by choriocarcinoma, embryonal carcinoma, and yolk sac tumor, while the lowest was observed in teratoma (p<0.0001). There was no association between GSTM1 expression in tumor tissue and patient/tumor characteristics. The low GSTM1 expression was associated with significantly better relapse-free survival compared with high GSTM1 (HR=0.50, 95% CI 0.23-1.09, p=0.03) but not overall survival (HR=0.61, 95% CI 0.24-1.54, p=0.22). Multivariate analysis showed that the prognostic value of GSTM1 was independent of the International Germ Cell Cancer Collaborative Group (IGCCCG) score. These data revealed the prognostic value of GSTM1 in GCTs, with a high GSTM1 expression associated with worse outcomes, suggesting that GSTM1 could be responsible, in part, for treatment resistance in GCTs.</p>\",\"PeriodicalId\":19266,\"journal\":{\"name\":\"Neoplasma\",\"volume\":\"71 4\",\"pages\":\"374-386\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neoplasma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4149/neo_2024_240609N249\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neoplasma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4149/neo_2024_240609N249","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

以顺铂为基础的化疗是治疗生殖细胞肿瘤(GCT)的主要方法。谷胱甘肽 S-转移酶(GST)是一种多态酶,可催化谷胱甘肽与烷化剂、铂化合物和化疗产生的自由基的结合,因此与治疗耐药性的产生有关。本研究旨在评估 GST mu 1(GSTM1)的表达水平及其与 GCT 患者治疗效果的关系。这项转化研究纳入了207名新确诊的GCT患者的肿瘤标本,以及顺铂敏感的GCT细胞系异种移植及其耐药变体,涵盖了GCT的所有组织学变体。GSTM1 的表达通过反转录定量 PCR 和使用单克隆抗体的免疫组织化学方法进行检测,并采用乘法快速评分(QS)法进行评分。GSTM1的表达与患者/肿瘤特征和治疗结果相关。精原细胞瘤的 GSTM1 表达量最高,其次是绒毛膜癌、胚胎癌和卵黄囊瘤,而畸胎瘤的 GSTM1 表达量最低(P<0.05)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Association between glutathione S-transferases M1 expression and treatment outcome in germ cell tumor patients.

Cisplatin-based chemotherapy is the mainstay in the treatment of germ cell tumors (GCTs). Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by chemotherapy and are thus implicated in developing treatment resistance. This study aimed to assess the expression level of GST mu 1 (GSTM1) and its association with treatment outcomes in patients with GCT. This translational study included tumor specimens from 207 patients with newly diagnosed GCTs, as well as cisplatin-sensitive GCT cell line xenografts and their resistant variants for all histological variants of GCTs. GSTM1 expression was detected by reverse transcription-quantitative PCR and immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method. GSTM1 expression was correlated with patient/tumor characteristics and treatment outcomes. The highest GSTM1 expression was observed in seminoma, followed by choriocarcinoma, embryonal carcinoma, and yolk sac tumor, while the lowest was observed in teratoma (p<0.0001). There was no association between GSTM1 expression in tumor tissue and patient/tumor characteristics. The low GSTM1 expression was associated with significantly better relapse-free survival compared with high GSTM1 (HR=0.50, 95% CI 0.23-1.09, p=0.03) but not overall survival (HR=0.61, 95% CI 0.24-1.54, p=0.22). Multivariate analysis showed that the prognostic value of GSTM1 was independent of the International Germ Cell Cancer Collaborative Group (IGCCCG) score. These data revealed the prognostic value of GSTM1 in GCTs, with a high GSTM1 expression associated with worse outcomes, suggesting that GSTM1 could be responsible, in part, for treatment resistance in GCTs.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Neoplasma
Neoplasma 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
238
审稿时长
3 months
期刊介绍: The journal Neoplasma publishes articles on experimental and clinical oncology and cancer epidemiology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信