Expression and Prognostic Significance of m6A-Related Genes in Lung Adenocarcinoma

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/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 m6Arelated 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 m6Arelated 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 m6Arelated genes METTL3, YTHDF1, and YTHDF2 could serve as novel biomarkers for the prognosis of LUAD.

SPATS2, negatively regulated by miR-145-5p, promotes hepatocellular carcinoma progression through regulating cell cycle

“…Public dataset acquisition and process were conducted as previously described 33 . The Cancer Genome Atlas (TCGA) database (http://gdc-portal.nci.nih.gov/) and Genotype-Tissue Expression (GTEX) database (https:// gtexportal.org/) were used to analyze the expression of SPATS2 in pan-cancers.…”

Comprehensive Analysis of the Prognostic Role and Mutational Characteristics of m6A-Related Genes in Lung Squamous Cell Carcinoma

“…Therefore, there also exist some differences in the significant m6A-related genes for patient outcomes. In LUAD, Zhang Y. et al (2020) demonstrated that METTL3, YTHDF1, and YTHDF2 were identified as prognostic genes and associated with better relapse-free survival (RFS) and OS. Li et al (2020) analyzed the TCGA database combined with the Genotype-Tissue Expression (GTEx) database and calculated the prognostic signature-based risk scores of RBM15, HNRNPC, and KIAA1429.…”

“…Recently, studies on the prognostic role of m6A genes have emerged, including LUAD ( Zhang Y. et al, 2020 ), renal cell carcinoma ( Gao et al, 2020 ), cervical cancer ( Yang et al, 2020 ), colorectal cancer ( Sun et al, 2020 ), and breast cancer ( Wei et al, 2020 ). However, few research focus on LUSC.…”

YTH Domain Proteins: A Family of m6A Readers in Cancer Progression

“…Based on this, the authors suggest that YTHDF2 can promote the growth of lung cancer by affecting the pentose phosphate pathway (PPP) ( 34 ). Recent studies have shown that YTHDF1 and YTHDF2 are highly expressed in lung adenocarcinoma and related to the prognosis of patients, but the specific mechanism remains unclear ( 74 ). Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database show that both YTHDF1 and YTHDF2 were highly expressed in lung adenocarcinoma ( 75 ).…”