Abstract
BackgroundThere have been limited treatment therapies for lung squamous cell carcinoma (LUSC). M6A-related genes may be the next therapeutic targets for LUSC. In this study, we explored the prognostic role and mutational characteristics of m6A-related genes in LUSC.MethodsLUSC gene expression data, mutational data, and corresponding clinical information were extracted from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) were identified, and the mutation characteristics of LUSC patients were explored. Then, m6A-related genes were extracted and the correlations among the genes were detected. Finally, the prognostic roles of the genes were investigated and the nomogram model was developed. Besides, the protein–protein interaction (PPI) network was used to explore the potential interactions among the genes.ResultsIn total, there are 551 LUSC samples enrolled in our study, containing 502 LUSC tumor samples and 49 adjacent normal LUSC samples, respectively. There were 2970 upregulated DEGs and 1806 downregulated DEGs were further explored. IGF2BP1 and RBM15 had significant co-occurrence frequency (p < 0.05). Besides, METTL14 and ZC3H13 or YTHDF3 also had significant co-occurrence frequency (p < 0.05). All the m6A-related genes represent the positive correlation. WTAP was identified as a prognostic gene in the TCGA database while YTHDC1 and YTHDF1 were identified as prognostic genes. In multivariate Cox analysis, YTHDF1, age, pN stage, pTNM stage, and smoking were all identified as significant prognostic factors for OS.ConclusionWe investigated the expression patterns and mutational characteristics of LUSC patients and identified three potential independent prognostic m6A-related genes (WTAP, YTHDC1, and YTHDF1) for OS in LUSC patients.
Highlights
MATERIALS AND METHODSLung cancer is one of the main causes of cancer-related deaths worldwide, with an approximate 5 year overall survival rate of 16–20% (Gu et al, 2017, 2018a,b, 2020a)
In order to identify the somatic mutations of lung squamous cell carcinoma (LUSC) patients, we analyzed the mutational data and visualized the data using the R package “maftools.” Besides, we further explored the somatic interactions among the m6A genes, along with the status of single-nucleotide polymorphism (SNP) and hypermutated genomic regions (Shi et al, 2018a,b; Zhang L. et al, 2020)
We explored the prognostic role of m6A-related genes and the mutational status of LUSC patients using the TCGA database, which suggest that WTAP, YTHDC1, m6A Related Genes in LUSC
Summary
MATERIALS AND METHODSLung cancer is one of the main causes of cancer-related deaths worldwide, with an approximate 5 year overall survival rate of 16–20% (Gu et al, 2017, 2018a,b, 2020a). Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) account for the vast majority, reaching about 55 and 30% of all NSCLCs, respectively (Gu et al, 2016). In lung cancer, METTL3 acts as an oncogene, which increases the growth, survival, and invasion of lung adenocarcinoma cells (Lin et al, 2016). This phenomenon suggests that m6A modifications and related genes may play important roles in tumor inhibition or tumorigenesis, which means that m6A modifications or m6A-related genes may be the tumor therapeutic targets, especially for LUSC (Pei et al, 2020). We explored the prognostic role and mutational characteristics of m6A-related genes in LUSC
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