N6-methylandenosine-related immune genes correlate with prognosis and immune landscapes in gastric cancer

Abstract

ObjectivesThis study aimed to probe into the significance of N6-methyladenosine (m6A)-related immune genes (m6AIGs) in predicting prognoses and immune landscapes of patients with gastric cancer (GC).MethodsThe clinical data and transcriptomic matrix of GC patients were acquired from The Cancer Genome Atlas database. The clinically meaningful m6AIGs were acquired by univariate Cox regression analysis. GC patients were stratified into different clusters via consensus clustering analysis and different risk subgroups via m6AIGs prognostic signature. The clinicopathological features and tumor microenvironment (TME) in the different clusters and different risk subgroups were explored. The predictive performance was evaluated using the KM method, ROC curves, and univariate and multivariate regression analyses. Moreover, we fabricated a nomogram based on risk scores and clinical risk characteristics. Biological functional analysis was performed based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The connectivity map was used to screen out potential small molecule drugs for GC patients.ResultsA total of 14 prognostic m6AIGs and two clusters based on 14 prognostic m6AIGs were identified. A prognostic signature based on 4 m6AIGs and a nomogram based on independent prognostic factors was constructed and validated. Different clusters and different risk subgroups were significantly correlated with TME scores, the distribution of immune cells, and the expression of immune checkpoint genes. Some malignant and immune biological processes and pathways were correlated with the patients with poor prognosis. Ten small molecular drugs with potential therapeutic effect were screened out.ConclusionsThis study revealed the prognostic role and significant values of m6AIGs in GC, which enhanced the understanding of m6AIGs and paved the way for developing predictive biomarkers and therapeutic targets for GC.

High expression of AlkB homolog 5 suppresses the progression of non‐small cell lung cancer by facilitating ferroptosis through m6A demethylation of SLC7A11

“…22,23 Indeed, both expression levels of m6A and m6A mediators are dysregulated in numerous cancers, which are extensively linked with drug resistance. 24 An increasing number of studies have demonstrated the suppressive action of ALKBH5 on the growth of a plethora of cancer cells, including pancreatic cancer 25 and bladder cancer. 26 Of note, the hard-done work of our peers has brought to light that tumor tissues from lung adenocarcinoma patients present low expression levels of ALKBH5 and ALKBH5 downregulation is indicative of a poorer overall survival, 27 which is in consistency with the bioinformatics analysis results in our study.…”

“…m6A is broadly regarded as the most predominant and abundant internal transcript modification in eukaryotic mRNA and possesses essential roles in cancer progression, and ALKBH5 is flagged as an m6A demethylase that responsible for eliminating m6A modification from RNAs and contributing to the maintenance of a dynamic equilibrium 22,23 . Indeed, both expression levels of m6A and m6A mediators are dysregulated in numerous cancers, which are extensively linked with drug resistance 24 . An increasing number of studies have demonstrated the suppressive action of ALKBH5 on the growth of a plethora of cancer cells, including pancreatic cancer 25 and bladder cancer 26 .…”