Runan Zhang, Haizhou Wang, Jun Xiao, Jie Lu, Menglin Li, You Zhou, He Sun, Lan Liu, Tizheng Huang, Qiu Zhao
{"title":"食管癌CAV1对肿瘤免疫微环境的影响及其预测免疫治疗应答的潜在价值","authors":"Runan Zhang, Haizhou Wang, Jun Xiao, Jie Lu, Menglin Li, You Zhou, He Sun, Lan Liu, Tizheng Huang, Qiu Zhao","doi":"10.1089/dna.2022.0025","DOIUrl":null,"url":null,"abstract":"<p><p>Caveolin-1 (<i>CAV1</i>) is one of the members of the caveolae, and the role of <i>CAV1</i> in esophageal cancer (ESCA) is not completely clear. In this study, we found that expression of <i>CAV1</i> was downregulated in ESCA in The Cancer Genome Atlas and the Genotype-Tissue Expression (GTEx) database and we also use immunohistochemistry of tissue microarray for verification. Then, we used bioinformatics methods to investigate the prognostic value of <i>CAV1</i>, influence on immune cell infiltration in tumor microenvironment (TME) and responding to immunotherapy in ESCA. Our result indicated that <i>CAV1</i> designs an inflamed TME in ESCA based on the evidence that <i>CAV1</i> positively correlated with immunomodulators, immune score, stomal score, cancer immunity cycles, tumor-infiltrating immune cells, T cell inflamed score, and immune checkpoints. Immunophenoscore, Tumor Immune Dysfunction and Exclusion algorithms, and the mutation analysis show that the downregulated <i>CAV1</i> expression indicated higher tumor mutation burden and higher rate of response to immune checkpoint inhibitors (ICIs) in the low-expression group. In a word, our study demonstrated the impact of <i>CAV1</i> to the TME in ESCA and it may be a new target for ESCA immunotherapy. In addition, the expression of <i>CAV1</i> can predict the clinical response to ICIs, which may provide clinical treatment guidance.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 1","pages":"27-42"},"PeriodicalIF":2.6000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"<i>CAV1</i> Impacts the Tumor Immune Microenvironment and Has Potential Value of Predicting Response to Immunotherapy in Esophageal Cancer.\",\"authors\":\"Runan Zhang, Haizhou Wang, Jun Xiao, Jie Lu, Menglin Li, You Zhou, He Sun, Lan Liu, Tizheng Huang, Qiu Zhao\",\"doi\":\"10.1089/dna.2022.0025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Caveolin-1 (<i>CAV1</i>) is one of the members of the caveolae, and the role of <i>CAV1</i> in esophageal cancer (ESCA) is not completely clear. In this study, we found that expression of <i>CAV1</i> was downregulated in ESCA in The Cancer Genome Atlas and the Genotype-Tissue Expression (GTEx) database and we also use immunohistochemistry of tissue microarray for verification. Then, we used bioinformatics methods to investigate the prognostic value of <i>CAV1</i>, influence on immune cell infiltration in tumor microenvironment (TME) and responding to immunotherapy in ESCA. Our result indicated that <i>CAV1</i> designs an inflamed TME in ESCA based on the evidence that <i>CAV1</i> positively correlated with immunomodulators, immune score, stomal score, cancer immunity cycles, tumor-infiltrating immune cells, T cell inflamed score, and immune checkpoints. Immunophenoscore, Tumor Immune Dysfunction and Exclusion algorithms, and the mutation analysis show that the downregulated <i>CAV1</i> expression indicated higher tumor mutation burden and higher rate of response to immune checkpoint inhibitors (ICIs) in the low-expression group. In a word, our study demonstrated the impact of <i>CAV1</i> to the TME in ESCA and it may be a new target for ESCA immunotherapy. In addition, the expression of <i>CAV1</i> can predict the clinical response to ICIs, which may provide clinical treatment guidance.</p>\",\"PeriodicalId\":11248,\"journal\":{\"name\":\"DNA and cell biology\",\"volume\":\"42 1\",\"pages\":\"27-42\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"DNA and cell biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/dna.2022.0025\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"DNA and cell biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/dna.2022.0025","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
Caveolin-1 (CAV1)是caveolae的成员之一,CAV1在食管癌(ESCA)中的作用尚不完全清楚。在本研究中,我们在The Cancer Genome Atlas和Genotype-Tissue expression (GTEx)数据库中发现,CAV1在ESCA中表达下调,并使用组织芯片免疫组化进行验证。然后,我们利用生物信息学方法研究CAV1的预后价值、对肿瘤微环境免疫细胞浸润(TME)的影响以及对ESCA免疫治疗的应答。我们的研究结果表明,基于CAV1与免疫调节剂、免疫评分、气孔评分、癌症免疫周期、肿瘤浸润免疫细胞、T细胞炎症评分和免疫检查点正相关的证据,CAV1设计了ESCA中炎症的TME。免疫表型评分、肿瘤免疫功能障碍和排斥算法以及突变分析显示,低表达组下调的CAV1表达表明更高的肿瘤突变负担和更高的免疫检查点抑制剂(ICIs)应答率。总之,我们的研究证明了CAV1对ESCA中TME的影响,它可能是ESCA免疫治疗的新靶点。此外,CAV1的表达可以预测ICIs的临床反应,为临床治疗提供指导。
CAV1 Impacts the Tumor Immune Microenvironment and Has Potential Value of Predicting Response to Immunotherapy in Esophageal Cancer.
Caveolin-1 (CAV1) is one of the members of the caveolae, and the role of CAV1 in esophageal cancer (ESCA) is not completely clear. In this study, we found that expression of CAV1 was downregulated in ESCA in The Cancer Genome Atlas and the Genotype-Tissue Expression (GTEx) database and we also use immunohistochemistry of tissue microarray for verification. Then, we used bioinformatics methods to investigate the prognostic value of CAV1, influence on immune cell infiltration in tumor microenvironment (TME) and responding to immunotherapy in ESCA. Our result indicated that CAV1 designs an inflamed TME in ESCA based on the evidence that CAV1 positively correlated with immunomodulators, immune score, stomal score, cancer immunity cycles, tumor-infiltrating immune cells, T cell inflamed score, and immune checkpoints. Immunophenoscore, Tumor Immune Dysfunction and Exclusion algorithms, and the mutation analysis show that the downregulated CAV1 expression indicated higher tumor mutation burden and higher rate of response to immune checkpoint inhibitors (ICIs) in the low-expression group. In a word, our study demonstrated the impact of CAV1 to the TME in ESCA and it may be a new target for ESCA immunotherapy. In addition, the expression of CAV1 can predict the clinical response to ICIs, which may provide clinical treatment guidance.
期刊介绍:
DNA and Cell Biology delivers authoritative, peer-reviewed research on all aspects of molecular and cellular biology, with a unique focus on combining mechanistic and clinical studies to drive the field forward.
DNA and Cell Biology coverage includes:
Gene Structure, Function, and Regulation
Gene regulation
Molecular mechanisms of cell activation
Mechanisms of transcriptional, translational, or epigenetic control of gene expression
Molecular Medicine
Molecular pathogenesis
Genetic approaches to cancer and autoimmune diseases
Translational studies in cell and molecular biology
Cellular Organelles
Autophagy
Apoptosis
P bodies
Peroxisosomes
Protein Biosynthesis and Degradation
Regulation of protein synthesis
Post-translational modifications
Control of degradation
Cell-Autonomous Inflammation and Host Cell Response to Infection
Responses to cytokines and other physiological mediators
Evasive pathways of pathogens.