在 PURE-01 研究中,通过不同的基因表达模式识别新辅助 Pembrolizumab 和根治性膀胱切除术后复发的患者。

IF 2.3 3区 医学 Q3 ONCOLOGY
Moritz J. Reike , Daniele Raggi , Chiara Mercinelli , Antonio Cigliola , Valentina Tateo , Damiano Alfio Patanè , Emanuele Crupi , Tiago Costa de Padua , Peter C. Black , Ewan A. Gibb , Andrea Necchi
{"title":"在 PURE-01 研究中,通过不同的基因表达模式识别新辅助 Pembrolizumab 和根治性膀胱切除术后复发的患者。","authors":"Moritz J. Reike ,&nbsp;Daniele Raggi ,&nbsp;Chiara Mercinelli ,&nbsp;Antonio Cigliola ,&nbsp;Valentina Tateo ,&nbsp;Damiano Alfio Patanè ,&nbsp;Emanuele Crupi ,&nbsp;Tiago Costa de Padua ,&nbsp;Peter C. Black ,&nbsp;Ewan A. Gibb ,&nbsp;Andrea Necchi","doi":"10.1016/j.clgc.2024.102214","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>The PURE-01 clinical trial reported the use of neoadjuvant treatment with pembrolizumab prior to radical cystectomy (RC) in patients with muscle-invasive bladder. Specific molecular subtypes and immune signatures were reported to be associated with a favorable survival. However, reports on the detailed tumor biology of patients relapsing after neoadjuvant pembrolizumab are lacking.</div></div><div><h3>Materials and Methods</h3><div>Microarray data from transurethral resection of the bladder tumor (TURBT; n = 102) and matched RC (N = 25) tissue from patients in PURE-01 who experience a disease relapse were analyzed, with gene expression signatures and molecular subtypes. The Kaplan–Meier method was used to estimate differences in patient outcomes. Immune-signatures were split by median for survival analysis. All significance testing used a two-sided t-test at a threshold of <em>P</em> &lt; .05.</div></div><div><h3>Results</h3><div>The study cohort consisted of 102 patients, of whom N = 19 (19%) experienced relapse. Molecular subtyping revealed that neuroendocrine-like tumors had the worst outcomes, while tumors classified as Claudin-low did show only one recurrence event. Differential gene expression analysis identified genes associated with relapse, including KRT20, H19, and immune-associated genes such as CXCL9 and CXCL11.</div></div><div><h3>Conclusion</h3><div>This study provides a detailed characterization of patients who relapsed after neoadjuvant pembrolizumab and RC and identifies distinct gene expression patterns associated with relapse. These findings may have implications for predicting patient response and guiding treatment decisions in the neoadjuvant setting.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102214"},"PeriodicalIF":2.3000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Distinct Gene Expression Patterns Identify Patients who Relapse After Neoadjuvant Pembrolizumab and Radical Cystectomy in the PURE-01 Study\",\"authors\":\"Moritz J. Reike ,&nbsp;Daniele Raggi ,&nbsp;Chiara Mercinelli ,&nbsp;Antonio Cigliola ,&nbsp;Valentina Tateo ,&nbsp;Damiano Alfio Patanè ,&nbsp;Emanuele Crupi ,&nbsp;Tiago Costa de Padua ,&nbsp;Peter C. Black ,&nbsp;Ewan A. Gibb ,&nbsp;Andrea Necchi\",\"doi\":\"10.1016/j.clgc.2024.102214\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><div>The PURE-01 clinical trial reported the use of neoadjuvant treatment with pembrolizumab prior to radical cystectomy (RC) in patients with muscle-invasive bladder. Specific molecular subtypes and immune signatures were reported to be associated with a favorable survival. However, reports on the detailed tumor biology of patients relapsing after neoadjuvant pembrolizumab are lacking.</div></div><div><h3>Materials and Methods</h3><div>Microarray data from transurethral resection of the bladder tumor (TURBT; n = 102) and matched RC (N = 25) tissue from patients in PURE-01 who experience a disease relapse were analyzed, with gene expression signatures and molecular subtypes. The Kaplan–Meier method was used to estimate differences in patient outcomes. Immune-signatures were split by median for survival analysis. All significance testing used a two-sided t-test at a threshold of <em>P</em> &lt; .05.</div></div><div><h3>Results</h3><div>The study cohort consisted of 102 patients, of whom N = 19 (19%) experienced relapse. Molecular subtyping revealed that neuroendocrine-like tumors had the worst outcomes, while tumors classified as Claudin-low did show only one recurrence event. Differential gene expression analysis identified genes associated with relapse, including KRT20, H19, and immune-associated genes such as CXCL9 and CXCL11.</div></div><div><h3>Conclusion</h3><div>This study provides a detailed characterization of patients who relapsed after neoadjuvant pembrolizumab and RC and identifies distinct gene expression patterns associated with relapse. These findings may have implications for predicting patient response and guiding treatment decisions in the neoadjuvant setting.</div></div>\",\"PeriodicalId\":10380,\"journal\":{\"name\":\"Clinical genitourinary cancer\",\"volume\":\"22 6\",\"pages\":\"Article 102214\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical genitourinary cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1558767324001848\",\"RegionNum\":3,\"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":"Clinical genitourinary cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1558767324001848","RegionNum":3,"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

目的:PURE-01 临床试验报告了在对肌肉浸润性膀胱患者进行根治性膀胱切除术(RC)前使用 pembrolizumab 进行新辅助治疗的情况。据报道,特定的分子亚型和免疫特征与良好的生存率有关。然而,关于新辅助治疗后复发的患者的详细肿瘤生物学情况还缺乏报道:分析了 PURE-01 中复发患者经尿道膀胱肿瘤切除术(TURBT;n = 102)和匹配的 RC(n = 25)组织的微阵列数据,以及基因表达特征和分子亚型。采用 Kaplan-Meier 法估计患者预后的差异。免疫特征按中位数分割,用于生存分析。所有显著性检验均采用双侧 t 检验,阈值为 P <.05:研究队列由102名患者组成,其中19人(19%)复发。分子亚型分析显示,神经内分泌样肿瘤的预后最差,而被归类为Claudin-low的肿瘤仅有一次复发。差异基因表达分析确定了与复发相关的基因,包括KRT20、H19和免疫相关基因,如CXCL9和CXCL11:这项研究详细描述了新辅助治疗彭博利珠单抗和RC后复发患者的特征,并确定了与复发相关的不同基因表达模式。这些发现可能会对预测患者反应和指导新辅助治疗决策产生影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Distinct Gene Expression Patterns Identify Patients who Relapse After Neoadjuvant Pembrolizumab and Radical Cystectomy in the PURE-01 Study

Purpose

The PURE-01 clinical trial reported the use of neoadjuvant treatment with pembrolizumab prior to radical cystectomy (RC) in patients with muscle-invasive bladder. Specific molecular subtypes and immune signatures were reported to be associated with a favorable survival. However, reports on the detailed tumor biology of patients relapsing after neoadjuvant pembrolizumab are lacking.

Materials and Methods

Microarray data from transurethral resection of the bladder tumor (TURBT; n = 102) and matched RC (N = 25) tissue from patients in PURE-01 who experience a disease relapse were analyzed, with gene expression signatures and molecular subtypes. The Kaplan–Meier method was used to estimate differences in patient outcomes. Immune-signatures were split by median for survival analysis. All significance testing used a two-sided t-test at a threshold of P < .05.

Results

The study cohort consisted of 102 patients, of whom N = 19 (19%) experienced relapse. Molecular subtyping revealed that neuroendocrine-like tumors had the worst outcomes, while tumors classified as Claudin-low did show only one recurrence event. Differential gene expression analysis identified genes associated with relapse, including KRT20, H19, and immune-associated genes such as CXCL9 and CXCL11.

Conclusion

This study provides a detailed characterization of patients who relapsed after neoadjuvant pembrolizumab and RC and identifies distinct gene expression patterns associated with relapse. These findings may have implications for predicting patient response and guiding treatment decisions in the neoadjuvant setting.
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
Clinical genitourinary cancer
Clinical genitourinary cancer 医学-泌尿学与肾脏学
CiteScore
5.20
自引率
6.20%
发文量
201
审稿时长
54 days
期刊介绍: Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.
×
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