{"title":"Characterization of immune landscape and prognostic value of IL-17-related signature in invasive breast cancer.","authors":"Wenge Dong, Xiaojie Gu, Jiejing Li, Zhigang Zhuang","doi":"10.21037/tcr-24-1632","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Recently, interleukin 17 (IL-17) has been found to play a critical role in the development of breast cancer. However, its prognostic significance in invasive breast cancer (IBC) remains unclear. This study aims to determine the role of IL-17-related signatures in IBC to identify novel therapeutic options.</p><p><strong>Methods: </strong>IBC data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used to identify IL-17-related prognostic genes. A predictive model was developed using TCGA data and validated using METABRIC data. The relationship between IL-17 scores and immune landscape, chemotherapy drug sensitivity [half maximal inhibitory concentration (IC50)], and immune checkpoint gene expression was analyzed. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate key gene expression in breast tumor and normal tissue samples.</p><p><strong>Results: </strong>The predictive model identified core IL-17-related prognostic genes and successfully estimated the prognosis of IBC patients. The model's validity was confirmed using METABRIC data. Patients with high IL-17 scores had worse overall survival (OS) compared to those with low IL-17 scores. Low IL-17 scores were associated with higher immune checkpoint gene expression and predicted enhanced responses to cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death protein 1 (PD-1) therapies. Patients with low IL-17 scores exhibited a higher abundance of immune microenvironment components. Furthermore, qRT-PCR confirmed the lower expression of <i>OR51E1, NDRG2, RGS2</i>, and <i>TSPAN7</i> in breast tumors compared to normal tissue.</p><p><strong>Conclusions: </strong>IL-17-related signatures are promising biomarkers for predicting the prognosis of IBC patients. These findings suggest that IL-17-related markers could be used to guide individualized therapeutic strategies, potentially improving outcomes for IBC patients.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"907-929"},"PeriodicalIF":1.5000,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912043/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-1632","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/26 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
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Abstract
Background: Recently, interleukin 17 (IL-17) has been found to play a critical role in the development of breast cancer. However, its prognostic significance in invasive breast cancer (IBC) remains unclear. This study aims to determine the role of IL-17-related signatures in IBC to identify novel therapeutic options.
Methods: IBC data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used to identify IL-17-related prognostic genes. A predictive model was developed using TCGA data and validated using METABRIC data. The relationship between IL-17 scores and immune landscape, chemotherapy drug sensitivity [half maximal inhibitory concentration (IC50)], and immune checkpoint gene expression was analyzed. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate key gene expression in breast tumor and normal tissue samples.
Results: The predictive model identified core IL-17-related prognostic genes and successfully estimated the prognosis of IBC patients. The model's validity was confirmed using METABRIC data. Patients with high IL-17 scores had worse overall survival (OS) compared to those with low IL-17 scores. Low IL-17 scores were associated with higher immune checkpoint gene expression and predicted enhanced responses to cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death protein 1 (PD-1) therapies. Patients with low IL-17 scores exhibited a higher abundance of immune microenvironment components. Furthermore, qRT-PCR confirmed the lower expression of OR51E1, NDRG2, RGS2, and TSPAN7 in breast tumors compared to normal tissue.
Conclusions: IL-17-related signatures are promising biomarkers for predicting the prognosis of IBC patients. These findings suggest that IL-17-related markers could be used to guide individualized therapeutic strategies, potentially improving outcomes for IBC patients.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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