Comprehensive Analysis of the Function, Immune Profiles, and Clinical Implication of m1A Regulators in Lung Adenocarcinoma

Abstract

BackgroundPrevious studies have demonstrated that transcriptional RNA methyladenosine modification significantly affects tumor initiation and progression. However, clinical implications of N1-methyladenosine (m1A) regulators and their effect on tumor immunity in lung adenocarcinoma (LUAD) are still poorly elucidated.MethodsHerein, the characteristics of somatic mutation, copy number variation (CNV), DNA methylation, and expression levels of m1A regulators were thoroughly analyzed. We classified 955 lung adenocarcinoma patients into different m1A modification patterns based on an unsupervised consensus clustering algorithm. We then calculated the differences in gene expression, prognosis outcomes, and immune profiles among different m1A clusters. Subsequently, we screened differently expressed genes (DEGs) related to prognosis among different m1A clusters. We identified m1A related gene clusters according to the prognosis-related different expressed genes. We further constructed a scoring standard named the m1A score and comprehensively analyzed the survival outcomes, clinical-pathological features, immune microenvironment, treatment responses of immunotherapy, and drug susceptibility in different m1A score groups.ResultsIn total, three different m1A modification patterns were identified, which contained cluster A, B, and C. Among them, cluster A processed the poorest clinical outcomes, the lowest immune cell infiltration rate, and the highest tumor purity score. Then, three m1A gene clusters (gene cluster A, B, C) were speculated. Subsequently, we combined m1A modification patterns and m1A gene cluster to classify lung adenocarcinoma patients into high and low m1A score groups. The low m1A score group was accompanied by higher mortality, higher tumor mutation burden (TMB) and genome mutation frequency, and lower programmed cell death-Ligand 1 (PD-L1) expression and tumor immune dysfunction and exclusion (TIDE) expression. Moreover, the m1A score exhibited positive correlation with almost all immune cells. Finally, common chemotherapeutic and targeted therapy agents exhibited obvious differences in drug susceptibility in different m1A score groups.ConclusionsCollectively, we explored the potential value of m1A regulators in the prognosis and treatment of lung adenocarcinoma in multiple dimensions and provided some preliminary basis for the follow-up study of m1A regulators in lung adenocarcinoma.

Development of m6A/m5C/m1A regulated lncRNA signature for prognostic prediction, personalized immune intervention and drug selection in LUAD

“…According to previous research, m1A methylation plays a significant role in tumour development and occurrence 18,89 . The study by Bao et al 90 . suggests that modulators of m1A can aid in the outcome prediction and treatment of LUAD, which provides some preliminary data for further studies on m1A modulators in LUAD.…”

“… 18 , 89 The study by Bao et al. 90 suggests that modulators of m1A can aid in the outcome prediction and treatment of LUAD, which provides some preliminary data for further studies on m1A modulators in LUAD. At present, there is no research on united m6A/m5C/m1A regulators in LUAD disease progression and prognosis, which deserves further attention.…”

“…88 According to previous research, m1A methylation plays a significant role in tumour development and occurrence. 18,89 The study by Bao et al 90 We utilized a pioneering research approach by incorporating the underutilized concepts of m6A, m5C and m1A. To increase the reliability of our conclusions, we employed an array of sophisticated bioinformatics statistical methods alongside real-time PCR validation of clinical samples.…”

Bioinformatics analysis of the role of RNA modification regulators in polycystic ovary syndrome

“…GSE34526 served as the test set, while GSE5850 and GSE98421 acted as veri cation sets. We identi ed 95 RNA modi cation-related genes (RMRGs) from relevant literature [15,16,17]. More information can be found in Table 1 and Table S1.…”

m1A Regulatory Gene signatures are associated with certain immune cell compositions of the tumor microenvironment and predict survival in kidney renal clear cell carcinoma

“…The function of each "reader" determines the endpoint of the modi ed RNA including splicing, stability and/or translation (16). Current studies suggest that m1A regulators' genetic mutation may affect the transcription and translation processes, leading to abnormal cell proliferation and tumorigenesis (17). In this case, according to Shi et al, m1A-related regulatory genes are essential for the tumorigenesis of hepatocellular carcinoma and have prognostic and diagnostic value (18).…”