m7G-Associated subtypes, tumor microenvironment, and validation of prognostic signature in lung adenocarcinoma.
m7G-Associated subtypes, tumor microenvironment, and validation of prognostic signature in lung adenocarcinoma.
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DOI：
10.3389/fgene.2022.954840
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发表时间：
2022
影响因子：
3.7
通讯作者：
Hong, Xiaohua
中科院分区：
文献类型：
--
作者：
Wang, Guangyao;Zhao, Mei;Li, Jiao;Li, Guosheng;Zheng, Fukui;Xu, Guanglan;Hong, Xiaohua
背景资料：7-甲基鸟苷（7-Methylguanosine，m7 G）是一种重要的基因转录后修饰，参与肿瘤的发生和发展。肿瘤微环境已被证明与肿瘤的进展和预后密切相关。然而，m7 G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。 研究方法：系统分析LUAD患者m7 G相关基因的遗传变异及其与预后和肿瘤微环境的关系。建立m7 G-Riskscore并分析其在疾病预后中的表现以及与患者对免疫疗法的反应的相关性。通过离体实验研究模型基因在蛋白质水平的表达。基于m7 G-Riskscore和几个显著的临床病理特征，最终获得列线图。 结果如下：从来自癌症基因组图谱和基因表达综合数据库的五个LUAD数据集获得m7 G相关基因，并确定其表达模式。基于m7 G相关基因，定义了三个LUAD簇。筛选三个基因簇的差异表达基因，并将LUAD患者进一步分为两个基因簇。研究表明，m7 G相关基因的改变与LUAD患者的临床病理特征、预后及肿瘤免疫浸润有关。获得了包括CAND 1、RRM 2和SLC 2A 1的m7 G-Riskscore，具有稳健和准确的预后性能。WB和细胞免疫荧光也显示CAND 1，RRM 2和SLC 2A 1在LUAD中的显著失调。此外，还建立了列线图，以提高m7 G-Riskscore的临床可行性。相关性分析显示，m7 G-Risk评分较低的患者具有较高的免疫和基质评分，对化疗药物和多靶向药物反应良好，存活时间较长。具有较高m7 G-Riskscore的患者倾向于遭受较高的肿瘤突变负荷。此外，m7 G-Riskscore表现出与免疫细胞浸润和癌症干性的显著相关性。 总结：本研究系统分析了m7 G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。本研究结果有助于从m7 G的角度更好地理解LUAD，也为LUAD的预后和治疗提供了新的思路。
Background: 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. Methods: 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 ex vivo experiments. A nomogram was finally obtained based on the m7G-Riskscore and several significant clinical pathological features. Results: 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. Conclusion: 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.
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影响因子：
2.7
作者：
Wang X;Pan L;Lu Q;Huang H;Feng C;Tao Y;Li Z;Hu J;Lai Z;Wang Q;Tang Z;Xie Y;Li T
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影响因子：
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作者：
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通讯作者：
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