Abstract

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common subtype of lung malignancy and is the leading cause of cancer-related mortalities worldwide. N6-methyladenosine (m6A), the most prevalent internal modification of mRNAs, plays crucial roles in regulating mRNA splicing, exportation, localization, translation, and stability. This study assessed the expression patterns and prognostic value of m6A-related genes in LUAD.

MATERIAL AND METHODS: The expression data of 509 LUAD samples and 20 normal samples were obtained from the Cancer Genome Atlas (TCGA) to determine the mRNA expression levels of m6A-related genomic targets. mRNA expression of 6 LUAD datasets was obtained from the Gene Expression Omnibus (GEO) repository. Subsequently, the Human Protein Atlas (HPA) and tissue microarray (TMA) cohort were used to verify the expression pattern of m6A-related genes at mRNA and protein level. The t test was used to analyze correlations between m6A-related genes and clinical features. Finally, survival analysis was performed to assess the prognostic value of m6A-related genes in LUAD patients.

RESULTS: We found that KIAA1429, RBM15, METTL3, HNRNPC, HNRNPA2B1, YTHDF1, and YTHDF2 were upregulated in TCGA-LUAD databases. The analysis of 7 GEO databases was consistent with the TCGA. YTHDF1 was overexpressed in LUAD patients and YTHDF2 was overexpressed in the great majority of cases. METTL3, YTHDF1, and YTHDF2 were associated with better OS and RFS.

CONCLUSIONS: m6A-related genes were differentially expressed in LUAD compared to matched normal patients. The m6A-related genes METTL3, YTHDF1, and YTHDF2 could serve as novel biomarkers for the prognosis of LUAD.

Keywords: Carcinoma, Non-Small-Cell Lung, Prognosis, Puromycin Aminonucleoside, Adenocarcinoma of Lung, Adenosine, Cohort Studies, Disease-Free Survival, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Lung Neoplasms, RNA, Messenger