Profile and diagnostic value of N6-methyladenosine-related mRNA regulators in colorectal adenoma and colorectal cancer.

BACKGROUND: N6-methyladenosine (m6A) modification is a key epigenetic modification involved in many diseases. However, the roles of m6A regulators in the progression of colorectal adenoma (CRA) or colorectal cancer (CRC) are still unclear fully. METHODS: Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) datasets GSE41657, GSE100179, and GSE117606. We analyzed differentially expressed m6A (DE-m6A) regulators and obtained two m6A patterns of CRA and CRC using the consensus clustering based on DE-m6A regulators. The differentially expressed genes (DEGs) between m6A patterns were subjected to gene set enrichment analysis (GSEA), and the m6A-related hub genes were evaluated by protein‒protein interaction (PPI) analysis. We screened important DE-m6A regulators using least absolute shrinkage and selection operation (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Receiver operating characteristic (ROC) curve was applied to analyze the clinical diagnostic value of hub genes and DE-m6A regulators, which were verified using quantitative real-time PCR. RESULTS: Fifteen DE-m6A regulators between controls and CRA patients and thirteen DE-m6A regulators between controls and CRC patients were identified with difference statistically. Two m6A patterns were obtained for CRA and CRC patients via consensus clustering based on DE-m6A regulators. DEGs were enriched in ribosomal structural components, signal receptor regulation, and mitochondrial structure and function. The five hub genes included TP53, EEF1A1, TBP, MARS1 and CCT7 in CRA, none in CRC were screened. Hub genes had good predictive effects on CRA and CRC. Six important DE-m6A regulators in CRA and one in CRC were screened out, and YTHDF1 on CRA or CRC, HNRNPA2B1 in only CRC had high diagnostic efficacy. Six important DE-m6A regulators were verified using quantitative real-time PCR. CONCLUSIONS: The m6A-related regulatory mode might have more important diagnostic value in CRA than in CRC.