Identification of Biomarkers of Ulcerative Colitis and Prediction of Therapeutic Drugs Based on Comprehensive Analysis of m6A Regulators

OBJECTIVE To explain the role of N6 methyladenosine(m6A) methylation regulators in ulcerative colitis(UC), and explore the relationship between m6A and UC immune regulation. Search for therapeutic targets and drugs of UC or biomarkers to assist clinical decision-making.

METHODS The GSE87466 data set was downloaded from the GEO database, and the differentially expressed m6A regulators were screened and verified by animal experiments. Random forest model was used to screen three m6A regulators as characteristic genes. A nomograph model was established to predict the risk of UC. Consensus clustering method is used to classify UC samples. ssGSEA analysis was used to evaluate the abundance of immune cells in samples and quantify immune infiltration. The coremine medical database, HERB database and CTD database were used to predict the traditional Chinese medicine and its components for the treatment of UC and carry out molecular docking verification.

RESULTS Compared with normal tissues, the expression levels of METTL3, HNRNPA2B1, IGF2BP1, YTHDF3 and LRPPRC in UC tissues were significantly different. GO enrichment analysis showed that m6A regulators were related to inflammatory immunity. The nomogram model based on LRPPRC, YTHDF3 and IGF2BP1 has good prediction ability. Immune infiltration analysis showed that the infiltration abundance of the remaining 22 immune cells in UC samples were significantly higher than that in normal samples. Cluster analysis showed that there were two different m6A modification patterns in UC, which had different immune infiltration characteristics and cytokine levels. Tripterygium wilfordii, vincristine and triptonide are most closely related to the differentially expressed m6A regulators. Molecular docking results show that they have good binding activity.

CONCLUSION The abnormal expression of m6A regulators are closely related to the occurrence and development of UC. LRPPRC, YTHDF3 and IGF2BP1 are expected to become biomarkers for the diagnosis and treatment of UC. Tripterygium wilfordii, vincristine, triptonide and other traditional Chinese medicine (TCM) or TCM components are expected to become potential drugs for the treatment of UC. This study provides new clues for clinical treatment and diagnosis and a reference direction for the development of new drugs against UC.