{"title":"MACC1 is a Potential Prognostic Biomarker for Cancer Immunotherapy in Lung Adenocarcinoma.","authors":"Changqie Pan, Zhiyuan Zhou, Jun Cao, Lemeng Zhang, Tianli Cheng, Haitao Li, Zhou Jiang, Danhui Huang, Dongqiang Zeng, Yongzhong Luo, Jianhua Wu","doi":"10.1093/carcin/bgaf015","DOIUrl":null,"url":null,"abstract":"<p><p>Our team previously reported that MACC1 levels are closely related to a variety of tumors and the efficacy of immune checkpoint blockade (ICB) therapy. However, the predictive value of MACC1 levels for lung adenocarcinoma (LUAD) immunotherapy has not been studied. This study aimed to investigate the predictive effect of the oncogene MACC1 on ICB reactivity in patients with LUAD. First, the expression patterns and clinical features of MACC1 in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were comprehensively evaluated using R packages. We subsequently assessed the correlations between MACC1 and immunological characteristics in the LUAD tumor microenvironment (TME) using the CIBERSORT algorithm. The results revealed that MACC1 overexpression was significantly correlated with 3 immune checkpoints, 14 tumor-infiltrating immune cells (TIICs), 9 immunomodulators, 5 anticancer immune process activities and 3 effector genes of TIICs in LUAD. Additionally, on the basis of the prognostic genes from LASSO analysis, we developed the MACC1-related Risk Score (MRRS), which can accurately predict the prognosis and response to cancer immunotherapy in LUAD patients (HR=3.50, AUC at 1, 2, and 3 years = 0.737, 0.744, and 0.724, respectively). Finally, in vivo experiments revealed that the combination of MACC1 silencing and PD-L1 inhibitors significantly inhibit tumor progression. These findings increase our understanding of MACC1 as a potential prognostic biomarker and potential therapeutic target for cancer immunotherapy. The MRRS may play a critical role in predicting the response of LUAD patients to ICB therapy.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Carcinogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/carcin/bgaf015","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Our team previously reported that MACC1 levels are closely related to a variety of tumors and the efficacy of immune checkpoint blockade (ICB) therapy. However, the predictive value of MACC1 levels for lung adenocarcinoma (LUAD) immunotherapy has not been studied. This study aimed to investigate the predictive effect of the oncogene MACC1 on ICB reactivity in patients with LUAD. First, the expression patterns and clinical features of MACC1 in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were comprehensively evaluated using R packages. We subsequently assessed the correlations between MACC1 and immunological characteristics in the LUAD tumor microenvironment (TME) using the CIBERSORT algorithm. The results revealed that MACC1 overexpression was significantly correlated with 3 immune checkpoints, 14 tumor-infiltrating immune cells (TIICs), 9 immunomodulators, 5 anticancer immune process activities and 3 effector genes of TIICs in LUAD. Additionally, on the basis of the prognostic genes from LASSO analysis, we developed the MACC1-related Risk Score (MRRS), which can accurately predict the prognosis and response to cancer immunotherapy in LUAD patients (HR=3.50, AUC at 1, 2, and 3 years = 0.737, 0.744, and 0.724, respectively). Finally, in vivo experiments revealed that the combination of MACC1 silencing and PD-L1 inhibitors significantly inhibit tumor progression. These findings increase our understanding of MACC1 as a potential prognostic biomarker and potential therapeutic target for cancer immunotherapy. The MRRS may play a critical role in predicting the response of LUAD patients to ICB therapy.
我们的团队之前报道了MACC1水平与多种肿瘤和免疫检查点阻断（ICB）治疗的疗效密切相关。然而，MACC1水平对肺腺癌（LUAD）免疫治疗的预测价值尚未得到研究。本研究旨在探讨致癌基因MACC1对LUAD患者ICB反应性的预测作用。首先，利用R软件包对MACC1在the Cancer Genome Atlas （TCGA）和Gene expression Omnibus （GEO）数据库中的表达模式和临床特征进行综合评估。随后，我们使用CIBERSORT算法评估了MACC1与LUAD肿瘤微环境（TME）中免疫学特征之间的相关性。结果显示，MACC1过表达与LUAD中3个免疫检查点、14个肿瘤浸润免疫细胞（TIICs）、9个免疫调节剂、5个抗癌免疫过程活性和3个TIICs效应基因显著相关。此外，在LASSO分析预后基因的基础上，我们制定了macc1相关风险评分（MRRS），可以准确预测LUAD患者的预后和对癌症免疫治疗的反应（HR=3.50, 1、2、3年的AUC分别= 0.737、0.744和0.724）。最后，体内实验显示MACC1沉默和PD-L1抑制剂联合使用可显著抑制肿瘤进展。这些发现增加了我们对MACC1作为癌症免疫治疗的潜在预后生物标志物和潜在治疗靶点的理解。MRRS可能在预测LUAD患者对ICB治疗的反应方面发挥关键作用。
期刊介绍：
Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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