Prognosis and immune infiltration analysis of m6A RNA methylation regulators in cutaneous melanoma and differential analysis with cuproptosis related genes

Abstract

Objective: N6-methyladenosine (m6A) modification and cuproptosis play essential roles in the pathogenesis of various malignant tumors. However, the predictive role of m6A regulators and cuproptosis-related genes in cutaneous melanoma (CM) remains unclear. In this study, the aim was not only to explore the role of m6A modification in CM, but also to investigate the differential expression of cuproptosis-related genes in different risk group. Methods: We obtained transcriptome data from the XENA and GTEx databases. Univariate Cox regression analysis was performed to investigate the relationship between m6A-related genes and the outcomes of CM. LASSO regression analysis was utilized to construct a risk model. Moreover, we analyzed immune cell infiltration using CIBERSORT algorithms. Finally, we evaluated the expression levels of cuproptosis-related genes in CM samples and performed RT-qPCR to validate the expression of cuproptosis-associated genes in melanoma cells after YTHDF3 knockdown. Results: All m6A-related genes differed in melanoma tissues and normal tissues and a prognostic signature was developed. Immune infiltration revealed that low-risk group patients had a higher level of CD8 + T cells, memory activated CD4 + T cells, activated NK cells and M1 Macrophages than high-risk group (P<0.05). Moreover, the cuproptosis-related genes MTF-1, PDHB and FDX1 were significantly negatively associated with risk score (P=0.0007, P=0.0057 and P=0.04, respectively). We also found that downregulation YTHDF3 in melanoma cells affected the expression of cuproptosis-related genes. (P<0.01 and P<0.05). Conclusion: Our study demonstrated the prognostic value of m6A-related genes and cuproptosis-related genes in CM, providing new predictive models and potential therapeutic targets for CM.