Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
Department of Radiation Oncology, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, China.
Dis Markers. 2022 Aug 23;2022:1829528. doi: 10.1155/2022/1829528. eCollection 2022.
Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, which is one of the most commonly diagnosed tumors and the leading causes of death from cancer around the world. Since RNA methylation is a posttranscriptional modification and affects so much biological progress, it is urged to explore the role of N6-methyladenosine (m6A) methylation in LUAD.
We explored the expression of 24 m6A methylation genes, as well as their correlations with LAG3 in 561 LUAD samples from TCGA. Consensus clustering was applied to m6A methylation genes, and two LUAD subgroups were identified. The expression of m6A genes was analyzed by the Wilcoxon test. KEGG and GO enrichment analyses were performed to indicate the pathway affected by differentially expressed genes in the two groups. A prognostic model based on LASSO regression using an eleven-m6A gene signature was constructed according to the expression of these genes. Receiver operating characteristic (ROC) curve was used to confirm the accuracy of the model in the TCGA cohort, as well as in the test cohort from the Gene Expression Omnibus (GEO) database.
Compared to cluster 1, cluster 2 showed poorer overall survival (OS) and higher LAG3 expression. In addition, KEGG and GO enrichment analyses indicated that differentially expressed genes are enriched in the immune response. We also observed that the expression of LAG3 is positively correlated with IGF2BP2, CBLL1, and HNRNPA2B1 and negatively correlated with YTHDF2, YTHDF3, and FTO. For patients in the TCGA cohort, the AUC score is 0.7, and the AUC score for the GSE50081 cohort is 0.675. Patients with lower risk scores exhibited better overall survival and lower expression of LAG3 than patients with higher risk scores.
In brief, our results indicated the important role of m6 methylation in affecting the tumor immune microenvironment and the survival of patients with LUAD. The m6A methylation gene signatures might serve as promising therapeutic targets and help the immunotherapy of LUAD in the future.
肺腺癌 (LUAD) 是肺癌最常见的组织学亚型，是全球最常见的诊断肿瘤之一，也是癌症死亡的主要原因。由于 RNA 甲基化是一种转录后修饰，并且影响着如此多的生物学进展，因此迫切需要探索 N6-甲基腺苷 (m6A) 甲基化在 LUAD 中的作用。
我们从 TCGA 的 561 例 LUAD 样本中探索了 24 个 m6A 甲基化基因的表达情况，以及它们与 LAG3 的相关性。应用共识聚类对 m6A 甲基化基因进行聚类，鉴定出两个 LUAD 亚组。采用 Wilcoxon 检验分析 m6A 基因的表达。通过 KEGG 和 GO 富集分析，研究两组中差异表达基因所影响的通路。根据这些基因的表达，构建了基于 LASSO 回归的十一基因 m6A 特征的预后模型。使用受试者工作特征 (ROC) 曲线来确认该模型在 TCGA 队列中的准确性，以及在来自基因表达综合数据库 (GEO) 的测试队列中的准确性。
与聚类 1 相比，聚类 2 的总生存期 (OS) 更差，LAG3 表达更高。此外，KEGG 和 GO 富集分析表明，差异表达基因富集在免疫反应中。我们还观察到 LAG3 的表达与 IGF2BP2、CBLL1 和 HNRNPA2B1 呈正相关，与 YTHDF2、YTHDF3 和 FTO 呈负相关。在 TCGA 队列中，AUC 评分为 0.7，在 GSE50081 队列中的 AUC 评分为 0.675。风险评分较低的患者的总生存期更好，LAG3 的表达也低于风险评分较高的患者。
总之，我们的研究结果表明 m6 甲基化在影响 LUAD 肿瘤免疫微环境和患者生存方面具有重要作用。m6A 甲基化基因特征可能成为有前途的治疗靶点，并有助于未来 LUAD 的免疫治疗。
