{"title":"Identification of an immune-related genes signature in lung adenocarcinoma to predict survival and response to immune checkpoint inhibitors.","authors":"Zeinab Davoodi-Moghaddam, Farideh Jafari-Raddani, Shahram Kordasti, Davood Bashash","doi":"10.1186/s43046-024-00236-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Although advances in immune checkpoint inhibitor (ICI) research have provided a new treatment approach for lung adenocarcinoma (LUAD) patients, their survival is still unsatisfactory, and there are issues in the era of response prediction to immunotherapy.</p><p><strong>Methods: </strong>Using bioinformatics methods, a prognostic signature was constructed, and its predictive ability was validated both in the internal and external datasets (GSE68465). We also explored the tumor-infiltrating immune cells, mutation profiles, and immunophenoscore (IPS) in the low-and high-risk groups.</p><p><strong>Results: </strong>As far as we are aware, this is the first study which introduces a novel prognostic signature model using BIRC5, CBLC, S100P, SHC3, ANOS1, VIPR1, LGR4, PGC, and IGKV4.1. According to multivariate analysis, the 9-immune-related genes (IRGs) signature provided an independent prognostic factor for the overall survival (OS). The low-risk group had better OS, and the tumor mutation burden (TMB) was significantly lower in this group. Moreover, the risk scores were negatively associated with the tumor-infiltrating immune cells, like CD8<sup>+</sup> T cells, macrophages, dendritic cells, and NK cells. In addition, the IPS were significantly higher in the low-risk group as they had higher gene expression of immune checkpoints, suggesting that ICIs could be a promising treatment option for low-risk LUAD patients.</p><p><strong>Conclusion: </strong>The combination of these 9-IRGs not only could efficiently predict overall survival of LUAD patients but also show a powerful association with the expression of immune checkpoints and response to ICIs based on IPS; hoping this model paves the way for better stratification and management of patients in clinical practice.</p>","PeriodicalId":17301,"journal":{"name":"Journal of the Egyptian National Cancer Institute","volume":"36 1","pages":"30"},"PeriodicalIF":2.1000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Egyptian National Cancer Institute","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s43046-024-00236-0","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Although advances in immune checkpoint inhibitor (ICI) research have provided a new treatment approach for lung adenocarcinoma (LUAD) patients, their survival is still unsatisfactory, and there are issues in the era of response prediction to immunotherapy.
Methods: Using bioinformatics methods, a prognostic signature was constructed, and its predictive ability was validated both in the internal and external datasets (GSE68465). We also explored the tumor-infiltrating immune cells, mutation profiles, and immunophenoscore (IPS) in the low-and high-risk groups.
Results: As far as we are aware, this is the first study which introduces a novel prognostic signature model using BIRC5, CBLC, S100P, SHC3, ANOS1, VIPR1, LGR4, PGC, and IGKV4.1. According to multivariate analysis, the 9-immune-related genes (IRGs) signature provided an independent prognostic factor for the overall survival (OS). The low-risk group had better OS, and the tumor mutation burden (TMB) was significantly lower in this group. Moreover, the risk scores were negatively associated with the tumor-infiltrating immune cells, like CD8+ T cells, macrophages, dendritic cells, and NK cells. In addition, the IPS were significantly higher in the low-risk group as they had higher gene expression of immune checkpoints, suggesting that ICIs could be a promising treatment option for low-risk LUAD patients.
Conclusion: The combination of these 9-IRGs not only could efficiently predict overall survival of LUAD patients but also show a powerful association with the expression of immune checkpoints and response to ICIs based on IPS; hoping this model paves the way for better stratification and management of patients in clinical practice.
背景:尽管免疫检查点抑制剂(ICI)研究的进展为肺腺癌(LUAD)患者提供了一种新的治疗方法,但他们的生存率仍不尽如人意,免疫疗法的反应预测时代也存在问题:方法:利用生物信息学方法构建了预后特征,并在内部和外部数据集(GSE68465)中验证了其预测能力。我们还探讨了低危和高危组的肿瘤浸润免疫细胞、突变特征和免疫表观评分(IPS):据我们所知,这是第一项使用 BIRC5、CBLC、S100P、SHC3、ANOS1、VIPR1、LGR4、PGC 和 IGKV4.1 建立新型预后特征模型的研究。根据多变量分析,9个免疫相关基因(IRGs)特征为总生存期(OS)提供了一个独立的预后因素。低风险组的OS较好,该组的肿瘤突变负荷(TMB)明显较低。此外,风险评分与肿瘤浸润免疫细胞(如 CD8+ T 细胞、巨噬细胞、树突状细胞和 NK 细胞)呈负相关。此外,低风险组的IPS明显较高,因为他们有较高的免疫检查点基因表达,这表明ICIs可能是低风险LUAD患者的一种有前途的治疗选择:结论:这9种IRGs的组合不仅能有效预测LUAD患者的总生存期,还能根据IPS显示出与免疫检查点表达和对ICIs反应的密切联系;希望这一模型能为临床实践中更好地对患者进行分层和管理铺平道路。
期刊介绍:
As the official publication of the National Cancer Institute, Cairo University, the Journal of the Egyptian National Cancer Institute (JENCI) is an open access peer-reviewed journal that publishes on the latest innovations in oncology and thereby, providing academics and clinicians a leading research platform. JENCI welcomes submissions pertaining to all fields of basic, applied and clinical cancer research. Main topics of interest include: local and systemic anticancer therapy (with specific interest on applied cancer research from developing countries); experimental oncology; early cancer detection; randomized trials (including negatives ones); and key emerging fields of personalized medicine, such as molecular pathology, bioinformatics, and biotechnologies.