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

Xuewen Wang; Chengfei Zhao; Dandan Huang; Zhoujie Liu; Mengmeng Liu; Fei Lin; Yingyu Lu; Jing Jia; Liqing Lin; Xinhua Lin; Huangyuan Li; Zhiwei Chen

doi:10.3389/fimmu.2022.923533

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

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

Authors

Xuewen Wang¹, Chengfei Zhao², Dandan Huang³, Zhoujie Liu⁴, Mengmeng Liu⁴, Fei Lin³, Yingyu Lu³, Jing Jia³, Liqing Lin³, Xinhua Lin^{3

5}, Huangyuan Li^{1

6}, Zhiwei Chen^{1

7}

Affiliations

¹ Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, China.
² Department of Pharmacy, School of Pharmacy and Medical Technology, Putian University, Putian, China.
³ Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, China.
⁴ Department of Pharmacy, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
⁵ Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Nano Medical Technology Research Institute, Fujian Medical University, Fuzhou, China.
⁶ Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China.
⁷ Fuzhou Center for Disease Control and Prevention, Fuzhou, China.

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.

Keywords: immune microenvironment; lung adenocarcinoma; m6A related genes; nomogram; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung* / drug therapy
Adenocarcinoma of Lung* / genetics
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / metabolism
Prognosis
ROC Curve
Survival Rate