Identification of prognostic m6A modification patterns and score system in melanoma patients.

ABSTRACT

N6-methyladenosine (m6A) is the most common modification on RNAs and LncRNAs. It plays an important role in cancer stem cell differentiation, T cell differentiation, and immune homeostasis. In this study, we explored the potential roles of m6A modification of RNA in melanoma and investigated the immune cell infiltration in tumor microenvironment in diverse m6Aclusters and different m6Ascore groups. A consensus clustering algorithm determined m6A modification patterns based on 14 m6A regulators, and further explored the biological functions and the connection with TME. An m6A-related gene signature (m6Ascore) was constructed based on m6A-related genes using principal component analysis. Three m6A modification patterns were identified based on 14 m6A regulators, named as m6Aclusters A-C. The prognosis of m6Acluster A was more favorable than m6Aclusters B and C, and it was more closely associated with immune regulation. To quantify the m6A modification patterns of individual tumor, an m6Ascore was constructed, and patients were classified into high and low m6Ascore groups. The low m6Ascore group, which had a favorable prognosis, was more relevant to immunology. The expression of PD-L1 was higher and the immunophenoscore (IPS) revealed stronger response to immunotherapy in the low m6Ascore group. This study identified 3 m6A modification patterns with different immune characteristics and constructed an m6Ascore system to predict prognosis and immunogenicity of patients, which is conducive to clinical prognosis judgment and individual treatment.