Bioinformatics analysis based on DNA methylation data identified in lung adenocarcinoma subgroups with different immune characteristics and clinical outcomes

Journal of Thoracic Disease

article

Ruilin Yu¹  Xiaoming Huang¹  Junqi Lin¹  Shaoming Lin¹  Guanle Shen¹  Wenbiao Chen¹ 

[1] Department of Respiratory Medicine, People’s Hospital of Longhua, The Affiliated Hospital of Southern Medical University;Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital

关键词: Lung adenocarcinoma (LUAD);    DNA methylation;    molecular subgroups;    immune cell infiltration;    genomic variation;   

DOI  :  10.21037/jtd-23-494

学科分类：呼吸医学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: DNA methylation can be used to predict clinical outcomes and improve the classification of tumors. The present study aimed to develop a new lung adenocarcinoma (LUAD) classification system according to the immune cell gene-related methylation sites and to reveal the survival outcomes, clinical characteristics, immune cell infiltration, stem cell characteristics, and genomic variations of each molecular subgroup. Methods: The DNA methylation sites of LUAD samples collected from The Cancer Genome Atlas (TCGA) database were analyzed, and the prognosis-related differential methylation sites (DMS) were screened. Consistent clustering of the samples was conducted using ConsensusClusterPlus, and the classification results were verified by principal component analysis (PCA). The survival and clinical results, immune cell infiltration, stemness, DNA mutation, and copy number variation (CNV) of each molecular subgroup were analyzed. Results: A total of 40 DMS were obtained by difference and univariate COX analyses, and the TCGA LUAD samples were divided into three subgroups: cluster 1 (C1), cluster 2 (C2), and cluster 3 (C3). Among these subgroups, the overall survival (OS) of C3 was significantly higher than that of C1 and C2. Compared with C1 and C3, C2 had the lowest innate immune cell and adaptive immune cell infiltration scores; the lowest stromal score, immune score, and iconic immune checkpoint expression; and the highest expression of messenger RNA (mRNA) expression-based stemness indices (mRNAsi), DNA methylation-based stemness index (mDNAsi), and tumor mutational burden (TMB). Conclusions: In this study, we proposed a LUAD typing system based on DMS, which was closely related to the survival, clinical features, immune characteristics, and genomic variations of LUAD, and may contribute to the development of personalized therapy for new specific subtypes.

【 授权许可】

Unknown