Characterization of m6A-Related Genes Landscape in Skin Cutaneous Melanoma to Aid Immunotherapy and Assess Prognosis

Abstract

Background: Skin cutaneous melanoma (SKCM) is the most malignant tumor among skin cancers. Immunotherapy has shown a great role in the advantageous prognosis of SKCM. However, only a small percentage of people can benefit from immunotherapy. To date, there has been insufficient evidence to reveal the prognostic value of m6A in SKCM and its relationship with the infiltration of immune cells and the efficacy of immunotherapy. Methods: Here, we synthetically analyzed 23 m6A regulators from SKCM samples collected from the TCGA and GEO databases. We defined three m6A modification patterns and constructed m6A scores using principal component analysis (PCA). Results: We found significant differences in overall survival (OS) and immune infiltration between different m6A subclusters. Besides, m6A score was positively correlated with regulatory T-cell and helper T-cell content, which may account for the association of high m6A scores with superior prognosis. Multivariate Cox regression analysis revealed that the m6A score was an independent prognostic indicator. Moreover, patients with high m6A scores showed a better response to immunotherapy, and this result was further validated in two independent immunotherapy cohorts receiving anti-PD-1/PD-L1 therapy. Conclusion:The findings suggested the m6A score can screen suitable candidates for immunotherapy and can predict immunotherapy response. This analysis of different m6A patterns in a large sample of SKCM expanded our understanding of TME and provided new ideas for prognostic assessment and personalized immunotherapy strategies for SKCM patients.

The Overexpression of SLC25A13 Predicts Poor Prognosis and Is Correlated with Immune Cell Infiltration in Patients with Skin Cutaneous Melanoma

“…Furthermore, SKCM treatment has been revolutionized with the approval of immune checkpoint inhibitors, which have a significant impact on the prognosis of patients with SKCM [ 36 ]. Nevertheless, only a small percentage of SKCM patients can benefit from immunotherapy [ 37 ]. Tumor immune cell infiltration can affect the sensitivity of immunotherapy, and higher immune cell infiltration scores showed a significant immune therapeutic advantage and clinical benefit [ 38 ].…”

Consensus Clustering and Survival-Related Genes of Cuproptosis in Cutaneous Melanoma

“…All data analyses used R software version 4.0.2. Statistical significance was defined as a P value of 0.05 [ 29 ].…”

The Potential Value of m6A RNA Methylation in the Development of Cancers Focus on Malignant Glioma

“…circIGF2BP3 reduces PD-L1 ubiquitination and subsequent proteasomal degradation by enhancing OTUB1 mRNA stability in a PKP3-dependent manner, leading to immune evasion of CD8+ T cell-mediated killing ( 169 ). It was found that there were significant differences in overall survival and immune cells infiltration between different m6A subgroups of cutaneous melanoma ( 170 ). The m6A score was positively associated with regulatory T-cell and helper T-cell content, which may explain why a high m6A score is associated with a better prognosis ( 170 ).…”

“…It was found that there were significant differences in overall survival and immune cells infiltration between different m6A subgroups of cutaneous melanoma ( 170 ). The m6A score was positively associated with regulatory T-cell and helper T-cell content, which may explain why a high m6A score is associated with a better prognosis ( 170 ). Furthermore, high m6A score patients presented a stronger response to novel immunotherapies, and two immune-related samples receiving anti-PD-1 or anti-PD-L1 therapy confirmed that patients in the high m6A score group had a better response to novel immunotherapy ( 170 ).…”