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一种新型 M6A 相关基因签名可影响肺腺癌的免疫状态并预测预后和药物敏感性。

A Novel M6A-Related Genes Signature Can Impact the Immune Status and Predict the Prognosis and Drug Sensitivity of Lung Adenocarcinoma.

机构信息

Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.

Department of Pharmacy, School of Pharmacy and Medical Technology, Putian University, Putian, China.

出版信息

Front Immunol. 2022 Jul 4;13:923533. doi: 10.3389/fimmu.2022.923533. eCollection 2022.

DOI:10.3389/fimmu.2022.923533
PMID:35860262
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9289247/
Abstract

Lung adenocarcinoma (LUAD) is a primary cause of cancer-related death around the world and has a poor outcome and high incidence. Treatment options are, however, restricted. One of the most critical factors in cancer and metastasis is the N6-methyladenine (m6A) alteration on RNA. This modification could alter gene expression and even function at numerous levels, such as the stability, translocation and translation of RNA splicing. This study aimed to construct an m6A-related genes signature to accurately predict the prognosis of LUAD patients. From TCGA datasets, the LUAD patient data and m6A-related genes were retrieved. LUAD patients' mutational features and differentially expressed genes (DEGs) were investigated. An univariate and LASSO model with m6A-related genes were constructed for the prediction of outcomes in LUAD. It was possible to develop a prognostic nomogram that could quantitatively predict LUAD patients' overall survival chances at 1, 3, and 5 years. Research into biological processes and cell pathways was carried out using GSEA. This study found six m6A-related DEGs in LUAD patients, and three of these DEGs(HNRNPC, IGFBP3 and IGF2BP1) were linked to the clinical outcomes of LUAD patients. We found that the overall survival rate for all LUAD patients with high-risk subgroup was considerably lower. According to ROC curves, the prognostic signature demonstrated a high degree of accuracy in predicting future outcomes. In addition, we created a novel nomogram achieved great accuracy with this one as well. The researchers also found that the novel signature might favorably modulate the immune response, and high-risk scores samples were more susceptible to numerous chemotherapeutic medicines. Overall, we developed a m6A-related gene prognostic signature that effectively predicted outcomes of LUAD patients and gave an immunological perspective for creating customized therapeutics.

摘要

肺腺癌 (LUAD) 是全球癌症相关死亡的主要原因，其预后差、发病率高。然而，治疗选择受到限制。在癌症和转移中，一个最关键的因素是 RNA 上的 N6-甲基腺嘌呤 (m6A) 改变。这种修饰可以在多个层面上改变基因表达甚至功能，例如 RNA 剪接的稳定性、易位和翻译。本研究旨在构建一个 m6A 相关基因特征，以准确预测 LUAD 患者的预后。从 TCGA 数据集获取 LUAD 患者数据和 m6A 相关基因。研究 LUAD 患者的突变特征和差异表达基因 (DEGs)。使用单变量和 LASSO 模型构建 m6A 相关基因预测 LUAD 患者结局。可以开发一个预后列线图，定量预测 LUAD 患者 1、3 和 5 年的总生存机会。使用 GSEA 进行生物过程和细胞途径的研究。本研究发现 LUAD 患者中有六个 m6A 相关 DEG，其中三个 DEG（HNRNPC、IGFBP3 和 IGF2BP1）与 LUAD 患者的临床结局相关。我们发现高危亚组所有 LUAD 患者的总体生存率明显较低。根据 ROC 曲线，预后特征在预测未来结局方面具有很高的准确性。此外，我们还创建了一个新的列线图，该图具有很高的准确性。研究人员还发现，该新特征可能有利于调节免疫反应，并且高危评分样本对许多化疗药物更敏感。总的来说，我们开发了一个 m6A 相关基因预后特征，该特征可有效预测 LUAD 患者的结局，并为制定个性化治疗提供免疫学视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a3/9289247/96abc273726e/fimmu-13-923533-g012.jpg
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