内质网应激相关基因对甲状腺癌预后、免疫治疗反应和药物敏感性的预测。

IF 3.2 4区 医学 Q3 IMMUNOLOGY
Journal of Immunotherapy Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI:10.1097/CJI.0000000000000554
Lu Zhao, Shuangmei Zhu, Wenxia Ye, Lifen Chen
{"title":"内质网应激相关基因对甲状腺癌预后、免疫治疗反应和药物敏感性的预测。","authors":"Lu Zhao, Shuangmei Zhu, Wenxia Ye, Lifen Chen","doi":"10.1097/CJI.0000000000000554","DOIUrl":null,"url":null,"abstract":"<p><p>ER stress has emerged as a promising target for cancer therapy. RNA sequencing data of patients with THCA were obtained from the TCGA database to identify differentially expressed genes associated with ER stress. Signature genes were selected through univariate Cox regression, LASSO, and multivariate Cox regression analyses. The predictive performance of the model was assessed using Kaplan-Meier survival analysis and ROC curves. GSEA was conducted to explore pathway enrichment between high-risk and low-risk groups. The immune landscape of risk groups was characterized using ssGSEA, ESTIMATE and CIBERSORT algorithms. Quantitative real-time PCR was employed to investigate the mRNA expression of the signature genes. Finally, immunotherapy response and potential drug sensitivity were evaluated. The prognostic model based on the signature genes ANK2, APOE, ERP27, FPR2, and NOS1, demonstrated robust predictive performance. GSEA results revealed distinct pathway enrichment patterns in the high-risk and low-risk groups. Furthermore, ssGSEA revealed that low-risk patients exhibited enhanced immune-related functions and increased immune cell infiltration. The RT-qPCR results revealed that in thyroid cancer cells, APOE and ERP27 expression levels were elevated, and ANK1, NOS1, and FPR2 expression levels were decreased. Immunotherapy, as well as Palbociclib and Perifosine, were predicted to be more effective for low-risk patients. Conversely, high-risk patients were more likely to benefit from Axitinib, Imatinib, Nilotinib, and Temsirolimus. This study identified 5 signature genes as potential biomarkers and therapeutic targets for THCA. These findings provide novel insights into the prognosis and targeted therapy of THCA, offering a foundation for furture clinical applications.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"159-172"},"PeriodicalIF":3.2000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of Endoplasmic Reticulum Stress-related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Sensitivity in Thyroid Cancer.\",\"authors\":\"Lu Zhao, Shuangmei Zhu, Wenxia Ye, Lifen Chen\",\"doi\":\"10.1097/CJI.0000000000000554\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>ER stress has emerged as a promising target for cancer therapy. RNA sequencing data of patients with THCA were obtained from the TCGA database to identify differentially expressed genes associated with ER stress. Signature genes were selected through univariate Cox regression, LASSO, and multivariate Cox regression analyses. The predictive performance of the model was assessed using Kaplan-Meier survival analysis and ROC curves. GSEA was conducted to explore pathway enrichment between high-risk and low-risk groups. The immune landscape of risk groups was characterized using ssGSEA, ESTIMATE and CIBERSORT algorithms. Quantitative real-time PCR was employed to investigate the mRNA expression of the signature genes. Finally, immunotherapy response and potential drug sensitivity were evaluated. The prognostic model based on the signature genes ANK2, APOE, ERP27, FPR2, and NOS1, demonstrated robust predictive performance. GSEA results revealed distinct pathway enrichment patterns in the high-risk and low-risk groups. Furthermore, ssGSEA revealed that low-risk patients exhibited enhanced immune-related functions and increased immune cell infiltration. The RT-qPCR results revealed that in thyroid cancer cells, APOE and ERP27 expression levels were elevated, and ANK1, NOS1, and FPR2 expression levels were decreased. Immunotherapy, as well as Palbociclib and Perifosine, were predicted to be more effective for low-risk patients. Conversely, high-risk patients were more likely to benefit from Axitinib, Imatinib, Nilotinib, and Temsirolimus. This study identified 5 signature genes as potential biomarkers and therapeutic targets for THCA. These findings provide novel insights into the prognosis and targeted therapy of THCA, offering a foundation for furture clinical applications.</p>\",\"PeriodicalId\":15996,\"journal\":{\"name\":\"Journal of Immunotherapy\",\"volume\":\" \",\"pages\":\"159-172\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Immunotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CJI.0000000000000554\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CJI.0000000000000554","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/26 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

内质网应激已成为癌症治疗的一个有希望的靶点。从TCGA数据库中获取THCA患者的RNA测序数据,鉴定与内质网应激相关的差异表达基因。通过单因素Cox回归、LASSO和多因素Cox回归分析选择特征基因。采用Kaplan-Meier生存分析和ROC曲线评估模型的预测性能。通过GSEA研究高危组和低危组之间的通路富集情况。使用ssGSEA、ESTIMATE和CIBERSORT算法对危险人群的免疫景观进行表征。采用实时荧光定量PCR法检测标记基因mRNA的表达情况。最后,评估免疫治疗反应和潜在的药物敏感性。基于标记基因ANK2、APOE、ERP27、FPR2和NOS1的预后模型显示出强大的预测性能。GSEA结果显示高危组和低危组的通路富集模式不同。此外,ssGSEA显示低风险患者表现出增强的免疫相关功能和增加的免疫细胞浸润。RT-qPCR结果显示,在甲状腺癌细胞中,APOE、ERP27表达水平升高,ANK1、NOS1、FPR2表达水平降低。免疫疗法以及Palbociclib和Perifosine预计对低风险患者更有效。相反,高风险患者更有可能从阿西替尼、伊马替尼、尼洛替尼和替西莫司中获益。本研究确定了5个标记基因作为THCA的潜在生物标志物和治疗靶点。这些发现为THCA的预后和靶向治疗提供了新的见解,为未来的临床应用奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of Endoplasmic Reticulum Stress-related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Sensitivity in Thyroid Cancer.

ER stress has emerged as a promising target for cancer therapy. RNA sequencing data of patients with THCA were obtained from the TCGA database to identify differentially expressed genes associated with ER stress. Signature genes were selected through univariate Cox regression, LASSO, and multivariate Cox regression analyses. The predictive performance of the model was assessed using Kaplan-Meier survival analysis and ROC curves. GSEA was conducted to explore pathway enrichment between high-risk and low-risk groups. The immune landscape of risk groups was characterized using ssGSEA, ESTIMATE and CIBERSORT algorithms. Quantitative real-time PCR was employed to investigate the mRNA expression of the signature genes. Finally, immunotherapy response and potential drug sensitivity were evaluated. The prognostic model based on the signature genes ANK2, APOE, ERP27, FPR2, and NOS1, demonstrated robust predictive performance. GSEA results revealed distinct pathway enrichment patterns in the high-risk and low-risk groups. Furthermore, ssGSEA revealed that low-risk patients exhibited enhanced immune-related functions and increased immune cell infiltration. The RT-qPCR results revealed that in thyroid cancer cells, APOE and ERP27 expression levels were elevated, and ANK1, NOS1, and FPR2 expression levels were decreased. Immunotherapy, as well as Palbociclib and Perifosine, were predicted to be more effective for low-risk patients. Conversely, high-risk patients were more likely to benefit from Axitinib, Imatinib, Nilotinib, and Temsirolimus. This study identified 5 signature genes as potential biomarkers and therapeutic targets for THCA. These findings provide novel insights into the prognosis and targeted therapy of THCA, offering a foundation for furture clinical applications.

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
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
×
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