Expression and Prognostic Value of m6A RNA Methylation-Related Genes in Thyroid Cancer

Iran J Public Health. 2023 Sep;52(9):1902-1916. doi: 10.18502/ijph.v52i9.13572.

Abstract

Background: N6-methyladenosine (m6A) methylation modification is involved in tumorigenesis and progression and can affect various stages of RNA processing. We aimed to determine m6A methylation modifications on a transcriptome-wide scale in thyroid cancer.

Methods: RNA samples from cancerous tissues and adjacent tissues extracted from patients with papillary thyroid carcinoma (PTC) from Hangzhou First People's Hospital, Zhejiang, China from January 2019 to January 2020 were used for m6A-sequencing. The biological function of differentially expressed genes (DEGs) was analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Correlation analysis between the results of transcriptome sequencing and m6A-sequencing was also performed. The key m6A immune-related genes were downloaded from Immport. LASSO regression was performed on the resulting genes to establish a prognostic risk model, which was verified by multivariate Cox proportional hazards regression analyses, receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis.

Results: An increase in m6A content in the total RNA of PTC was observed. A total of 123 genes with significant differential expression and differential methylation sites in thyroid cancer were selected, related to protein digestion and absorption, linoleic acid metabolism, legionellosis and alpha-linolenic acid metabolism. Seven genes (GDNF, EBI3, CCL2, BMP5, TGFB2, CGB3 and RLN2) were found to be predictive of PTC.

Conclusion: We analyzed the expression, enrichment pathways and functions of m6A methylation-related genes in the whole transcriptome of thyroid cancer and provided a prognostic risk model for thyroid cancer patients.

Keywords: Methylated RNA immunoprecipitation sequencing; N6-methyladenosine; Thyroid cancer.