{"title":"肾癌患者il - 3信号通路相关基因与免疫检查点抑制剂疗效的相关性","authors":"Shuang Hou, Tianqi Gu, Ying Shi, Yushan Huang, Jiarong Yao, Peng Luo, Manming Cao, Jian Zhang, Anqi Lin, Weiliang Zhu","doi":"10.3233/CBM-230226","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>There is a lack of effective biomarkers that predict immunotherapy efficacy in clear cell renal cell carcinoma(KIRC).</p><p><strong>Objective: </strong>We aimed to identify biomarkers that would predict the efficacy of KIRC treatment with immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>Cohort data of KIRC patients with somatic mutations, mRNA expression and survival data from The Cancer Genome Atlas (TCGA) database and immunotherapy cohort and Genomics of Drug Sensitivity in Cancer (GDSC) database were analyzed and divided into interleukin 3 (IL3) pathway-related genes high expression (IL3-High) and IL3 pathway-related genes low expression (IL3-Low) groups according to pathway expression status to assess the relationship between the IL3 pathway-related genes activation status and the prognosis of KIRC patients treated with ICIs. The data were validated by immunohistochemistry experiments, and possible mechanisms of action were explored at the level of gene mutation landscape, immune microenvironment characteristics, transcriptome and copy number variation(CNV) characteristicsRESULTS: The IL3 pathway-related genes was an independent predictor of the efficacy of ICIs in KIRC patients, and the IL3-High group had a longer overall survival (OS); KIRC patients in the IL3-High group had increased levels of chemokines, cytolysis, immune checkpoint gene expression and abundant immunity. The IL3-Low group had poor immune cell infiltration and significant downregulation of complement activation, cytophagy, B-cell activation, and humoral immune response pathways. The high group was more sensitive to targeted drugs of some signaling pathways, and its efficacy in combining these drugs with immunity has been predicted in the published literature.</p><p><strong>Conclusion: </strong>The IL3 pathway-related genes can be used as a predictor of the efficacy of ICIs in KIRC. The IL3 pathway-related genes may affect the therapeutic efficacy of ICIs by affecting the expression of immune-related molecules, immune cell infiltration, and the level of immune response pathways.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Correlation between IL3 signaling pathway-related genes and immune checkpoint inhibitor efficacy in patients with renal cell carcinoma.\",\"authors\":\"Shuang Hou, Tianqi Gu, Ying Shi, Yushan Huang, Jiarong Yao, Peng Luo, Manming Cao, Jian Zhang, Anqi Lin, Weiliang Zhu\",\"doi\":\"10.3233/CBM-230226\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>There is a lack of effective biomarkers that predict immunotherapy efficacy in clear cell renal cell carcinoma(KIRC).</p><p><strong>Objective: </strong>We aimed to identify biomarkers that would predict the efficacy of KIRC treatment with immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>Cohort data of KIRC patients with somatic mutations, mRNA expression and survival data from The Cancer Genome Atlas (TCGA) database and immunotherapy cohort and Genomics of Drug Sensitivity in Cancer (GDSC) database were analyzed and divided into interleukin 3 (IL3) pathway-related genes high expression (IL3-High) and IL3 pathway-related genes low expression (IL3-Low) groups according to pathway expression status to assess the relationship between the IL3 pathway-related genes activation status and the prognosis of KIRC patients treated with ICIs. The data were validated by immunohistochemistry experiments, and possible mechanisms of action were explored at the level of gene mutation landscape, immune microenvironment characteristics, transcriptome and copy number variation(CNV) characteristicsRESULTS: The IL3 pathway-related genes was an independent predictor of the efficacy of ICIs in KIRC patients, and the IL3-High group had a longer overall survival (OS); KIRC patients in the IL3-High group had increased levels of chemokines, cytolysis, immune checkpoint gene expression and abundant immunity. The IL3-Low group had poor immune cell infiltration and significant downregulation of complement activation, cytophagy, B-cell activation, and humoral immune response pathways. The high group was more sensitive to targeted drugs of some signaling pathways, and its efficacy in combining these drugs with immunity has been predicted in the published literature.</p><p><strong>Conclusion: </strong>The IL3 pathway-related genes can be used as a predictor of the efficacy of ICIs in KIRC. The IL3 pathway-related genes may affect the therapeutic efficacy of ICIs by affecting the expression of immune-related molecules, immune cell infiltration, and the level of immune response pathways.</p>\",\"PeriodicalId\":56320,\"journal\":{\"name\":\"Cancer Biomarkers\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Biomarkers\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3233/CBM-230226\",\"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":"Cancer Biomarkers","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3233/CBM-230226","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
背景:目前缺乏预测透明细胞肾细胞癌(KIRC)免疫治疗效果的有效生物标志物。目的:我们旨在确定生物标志物，以预测免疫检查点抑制剂(ICIs)治疗KIRC的疗效。方法:KIRC体细胞突变患者的队列数据分析来自Cancer Genome Atlas (TCGA)数据库和immunotherapy cohort and Genomics of Drug Sensitivity in Cancer (GDSC)数据库的mRNA表达和生存数据，根据通路表达状态将其分为白细胞介素3 (interleukin 3, IL3)通路相关基因高表达组(IL3- high)和IL3通路相关基因低表达组(IL3- low)，评估IL3通路相关基因激活状态与ICIs治疗KIRC患者预后的关系。通过免疫组织化学实验对数据进行验证，并从基因突变景观、免疫微环境特征、转录组和拷贝数变异(CNV)特征等层面探讨可能的作用机制。结果:IL3通路相关基因是KIRC患者ICIs疗效的独立预测因子，IL3- high组总生存期(OS)更长;IL3-High组KIRC患者的趋化因子水平、细胞溶解水平、免疫检查点基因表达水平升高，免疫力丰富。IL3-Low组免疫细胞浸润差，补体活化、细胞吞噬、b细胞活化、体液免疫反应通路明显下调。高剂量组对某些信号通路的靶向药物更敏感，已发表文献预测其与免疫联合用药的疗效。结论:il - 3通路相关基因可作为ICIs治疗KIRC疗效的预测因子。il - 3通路相关基因可能通过影响免疫相关分子的表达、免疫细胞浸润、免疫应答通路水平等影响ICIs的治疗效果。
Correlation between IL3 signaling pathway-related genes and immune checkpoint inhibitor efficacy in patients with renal cell carcinoma.
Background: There is a lack of effective biomarkers that predict immunotherapy efficacy in clear cell renal cell carcinoma(KIRC).
Objective: We aimed to identify biomarkers that would predict the efficacy of KIRC treatment with immune checkpoint inhibitors (ICIs).
Methods: Cohort data of KIRC patients with somatic mutations, mRNA expression and survival data from The Cancer Genome Atlas (TCGA) database and immunotherapy cohort and Genomics of Drug Sensitivity in Cancer (GDSC) database were analyzed and divided into interleukin 3 (IL3) pathway-related genes high expression (IL3-High) and IL3 pathway-related genes low expression (IL3-Low) groups according to pathway expression status to assess the relationship between the IL3 pathway-related genes activation status and the prognosis of KIRC patients treated with ICIs. The data were validated by immunohistochemistry experiments, and possible mechanisms of action were explored at the level of gene mutation landscape, immune microenvironment characteristics, transcriptome and copy number variation(CNV) characteristicsRESULTS: The IL3 pathway-related genes was an independent predictor of the efficacy of ICIs in KIRC patients, and the IL3-High group had a longer overall survival (OS); KIRC patients in the IL3-High group had increased levels of chemokines, cytolysis, immune checkpoint gene expression and abundant immunity. The IL3-Low group had poor immune cell infiltration and significant downregulation of complement activation, cytophagy, B-cell activation, and humoral immune response pathways. The high group was more sensitive to targeted drugs of some signaling pathways, and its efficacy in combining these drugs with immunity has been predicted in the published literature.
Conclusion: The IL3 pathway-related genes can be used as a predictor of the efficacy of ICIs in KIRC. The IL3 pathway-related genes may affect the therapeutic efficacy of ICIs by affecting the expression of immune-related molecules, immune cell infiltration, and the level of immune response pathways.
期刊介绍：
Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion.
The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
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