Wang Guangyao, Zhao Mei, Li Jiao, Li Guosheng, Zheng Fukui, Xu Guanglan, Hong Xiaohua
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, China.
Department of Intensive Care Unit, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, China.
Front Genet. 2022 Aug 10;13:954840. doi: 10.3389/fgene.2022.954840. eCollection 2022.
7-Methylguanosine (m7G) is an important posttranscriptional modification that regulates gene expression and is involved in tumorigenesis and development. Tumor microenvironment has been proven to be highly involved in tumor progression and prognosis. However, how m7G-associated genes affect the tumor microenvironment of patients with lung adenocarcinoma (LUAD) remains to be further clarified. The genetic alterations of m7G-associated genes and their associations with the prognosis and tumor microenvironment in LUAD patients were systemically analyzed. An m7G-Riskscore was established and analyzed for its performance in disease prognosis and association with patient response to immunotherapy. Expression of the model genes at the protein level was investigated through experiments. A nomogram was finally obtained based on the m7G-Riskscore and several significant clinical pathological features. m7G-Associated genes were obtained from five LUAD datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases, and their expression pattern was determined. Based on the m7G-associated genes, three LUAD clusters were defined. The differentially expressed genes from the three clusters were screened and used to further divide the LUAD patients into two gene clusters. It was demonstrated that the alterations of m7G-associated genes were associated with the clinical pathological features, prognosis, and tumor immune infiltration in LUAD patients. An m7G-Riskscore including CAND1, RRM2, and SLC2A1 was obtained with robust and accurate prognostic performance. WB and cell immunofluorescence also showed significant dysregulation of CAND1, RRM2, and SLC2A1 in LUAD. In addition, a nomogram was established to improve the clinical feasibility of the m7G-Riskscore. Correlation analysis revealed that patients with a lower m7G-Riskscore had higher immune and stromal scores, responded well to chemotherapeutics and multiple targeted drugs, and survived longer. Patients with a higher m7G-Riskscore tended to suffer from a higher tumor mutation burden. Furthermore, the m7G-Riskscore exhibited significant associations with immune cell infiltration and cancer stemness. This study systemically analyzed m7G-associated genes and identified their potential role in tumor microenvironment and prognosis in patients with LUAD. The findings of the present study may help better understand LUAD from the m7G perspective and also provide a new thought toward the prognosis and treatment of LUAD.
7-甲基鸟苷（m7G）是一种重要的转录后修饰，可调节基因表达，并参与肿瘤的发生和发展。肿瘤微环境已被证明与肿瘤进展和预后密切相关。然而，m7G相关基因如何影响肺腺癌（LUAD）患者的肿瘤微环境仍有待进一步阐明。本研究系统分析了LUAD患者中m7G相关基因的遗传改变及其与预后和肿瘤微环境的关系。建立了m7G风险评分，并分析了其在疾病预后中的表现以及与患者免疫治疗反应的相关性。通过实验研究了模型基因在蛋白质水平的表达。最终基于m7G风险评分和几个重要的临床病理特征获得了列线图。从癌症基因组图谱（The Cancer Genome Atlas）和基因表达综合数据库（Gene Expression Omnibus）的五个LUAD数据集中获取m7G相关基因，并确定其表达模式。基于m7G相关基因，定义了三个LUAD簇。筛选出这三个簇中差异表达的基因，并用于进一步将LUAD患者分为两个基因簇。结果表明，m7G相关基因的改变与LUAD患者的临床病理特征、预后和肿瘤免疫浸润相关。获得了一个包含CAND1、RRM2和SLC2A1的m7G风险评分，其具有稳健且准确的预后性能。蛋白质免疫印迹（WB）和细胞免疫荧光也显示LUAD中CAND1、RRM2和SLC2A1存在明显失调。此外，建立了列线图以提高m7G风险评分的临床可行性。相关性分析显示，m7G风险评分较低的患者具有较高的免疫和基质评分，对化疗药物和多种靶向药物反应良好，生存期更长。m7G风险评分较高的患者往往具有较高的肿瘤突变负担。此外，m7G风险评分与免疫细胞浸润和癌症干性显著相关。本研究系统分析了m7G相关基因，并确定了它们在LUAD患者肿瘤微环境和预后中的潜在作用。本研究结果可能有助于从m7G角度更好地理解LUAD，并为LUAD的预后和治疗提供新的思路。
