Development and Validation of a Novel Defined 7-Methylguanosine-Related Gene Signature to Prognose Thyroid Cancer Outcomes

Abstract

Background: The modification of 7-methylguanosine (m7G) is a type of tRNA modification closely associated with cancer. Nevertheless, the capacity of m⁷G-related genetic expression to prognose cancer outcomes remains elusive in thyroid cancer. Methods: Overall, among the 21 differentially expressed genes (DEGs) observed between thyroid cancer and nominal tissue, 4 were relevant to the overall survival (OS) (p < 0.05). A risk signature via least absolute shrinkage and selection operator (LASSO) Cox regressive analyses was developed in the The Cancer Genome Atlas (TCGA) cohort. In addition, reverse-transcription quantitative polymerase chain reaction (RT-qPCR) determined the mRNA expression of genes in the model, and the risk signature according to the genetic expression was validated. Finally, the functional enrichment method was used to investigate the underlying causal links. Results: A 4-gene signature (nudix hydrolase 16, NUDT16;Eukaryotic translation initiation factor 4E, EIF4E;Gem nuclear organelle associated protein 5, GEMIN5;Decapping mRNA 2, DCP2) showed powerful prediction ability in both TCGA and validation cohorts. The median risk score of the 4-gene signature was considered to classify patients into risk_high group and risk_low group. Sufferers in risk_low group had a higher OS relative to risk_high group (p < 0.01). According to Cox regression analysis, risk score could independently predict thyroid cancer patients’ OS. The receiver operating characteristic (ROC) method assisted in verifying the predictive ability of the genetic signature. Subsequently, we discovered that the 4 genes exhibited aberrant expression between thyroid cancer and healthy specimens. Function analyses revealed that both groups showed diverse immune status. Conclusions: The predictive ability of the 4-gene signature was proven. Overall, m⁷G-associated genes are valid to prognosis thyroid cancer outcomes and can be an underlying treatment target.