Li Zhouhua, Wang Wenjun, Wu Juan, Ye Xiaoqun
Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Front Med (Lausanne). 2022 Aug 24;9:962972. doi: 10.3389/fmed.2022.962972. eCollection 2022.
Lung adenocarcinoma (LUAD) is one of the most frequent causes of tumor-related mortality worldwide. Recently, the role of N7-methylguanosine (mG) in tumors has begun to receive attention, but no investigation on the impact of mG on LUAD. This study aims to elucidate the significance of mG on the prognosis and immunotherapy in LUAD.
Consensus clustering was employed to determine the molecular subtype according to mG-related regulators extracted from The Cancer Genome Atlas (TCGA) database. Survival, clinicopathological features and tumor mutational burden (TMB) analysis were applied to research molecular characteristics of each subtype. Subsequently, "limma" package was used to screen differentially expressed genes (DEGs) between subtypes. In the TCGA train cohort ( = 245), a prognostic signature was established by univariate Cox regression, lasso regression and multivariate Cox regression analysis according to DEGs and survival analysis was employed to assess the prognosis. Then the prognostic value of the signature was verified by TCGA test cohort ( = 245), TCGA entire cohort ( = 490) and GSE31210 cohort ( = 226). Moreover, the association among immune infiltration, clinical features and the signature was investigated. The immune checkpoints, TMB and tumor immune dysfunction and exclusion (TIDE) were applied to predict the immunotherapy response.
Two novel molecular subtypes (C1 and C2) of LUAD were identified. Compared to C2 subtype, C1 subtype had poorer prognosis and higher TMB. Subsequently, the signature (called the "mG score") was constructed according to four key genes (, , , and ). The distribution of mG score were significantly different between two molecular subtypes. The patients with lower mG score had better prognosis in TCGA train cohort and three verification cohort. The mG score was intensively related to immune infiltration. Compared with the lower score, the higher mG score was related to remarkable upregulation of the PD-1 and PD-L1, the higher TMB and the lower TIDE score.
This study established a mG-related signature for predicting prognosis and immunotherapy in LUAD, which may contribute to the development of new therapeutic strategies for LUAD.
肺腺癌（LUAD）是全球肿瘤相关死亡的最常见原因之一。最近，N7-甲基鸟苷（mG）在肿瘤中的作用开始受到关注，但尚未有关于mG对LUAD影响的研究。本研究旨在阐明mG对LUAD预后和免疫治疗的意义。
采用共识聚类法，根据从癌症基因组图谱（TCGA）数据库中提取的mG相关调节因子确定分子亚型。应用生存分析、临床病理特征和肿瘤突变负荷（TMB）分析来研究各亚型的分子特征。随后，使用“limma”软件包筛选亚型之间的差异表达基因（DEG）。在TCGA训练队列（n = 245）中，根据DEG通过单变量Cox回归、套索回归和多变量Cox回归分析建立预后特征，并采用生存分析评估预后。然后通过TCGA测试队列（n = 245）、TCGA完整队列（n = 490）和GSE31210队列（n = 226）验证该特征的预后价值。此外，还研究了免疫浸润、临床特征与该特征之间的关联。应用免疫检查点、TMB和肿瘤免疫功能障碍与排除（TIDE）来预测免疫治疗反应。
鉴定出LUAD的两种新分子亚型（C1和C2）。与C2亚型相比，C1亚型预后较差且TMB较高。随后，根据四个关键基因（，，，和）构建了特征（称为“mG评分”）。两种分子亚型之间mG评分的分布有显著差异。在TCGA训练队列和三个验证队列中，mG评分较低的患者预后较好。mG评分与免疫浸润密切相关。与较低评分相比，较高的mG评分与PD-1和PD-L1的显著上调、较高的TMB和较低的TIDE评分相关。
本研究建立了一种与mG相关的特征，用于预测LUAD的预后和免疫治疗，这可能有助于开发LUAD的新治疗策略。
