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Identification of prognostic m6A modification patterns and score system in melanoma patients
Feixiang Wang1, Peijie Chen, Si Ouyang
1Medical Oncology Department, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangdong, Guangzhou, China.
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.
Insights
N6-methyladenosine (m6A) RNA modifications influence melanoma and immune responses. This study defined m6A patterns and developed an m6Ascore to predict patient prognosis and immunotherapy effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- N6-methyladenosine (m6A) is the most prevalent RNA modification, crucial for cellular processes including differentiation and immune homeostasis.
- m6A modifications are increasingly recognized for their roles in cancer development and progression.
Purpose of the Study:
- To investigate the role of RNA m6A modification in melanoma.
- To analyze immune cell infiltration within the tumor microenvironment based on m6A modification patterns and scores.
- To develop a predictive model for prognosis and immunogenicity in melanoma patients.
Main Methods:
- Consensus clustering of 14 m6A regulators to define m6A modification patterns (m6Aclusters).
- Construction of an m6A-related gene signature (m6Ascore) using principal component analysis.
- Analysis of immune cell infiltration, PD-L1 expression, and immunophenoscore (IPS) in relation to m6Aclusters and m6Ascore groups.
Main Results:
- Three distinct m6Aclusters (A-C) were identified, with m6Acluster A showing a more favorable prognosis and stronger association with immune regulation.
- An m6Ascore system classified patients into high and low groups; the low m6Ascore group had a favorable prognosis and was linked to enhanced immunology.
- The low m6Ascore group exhibited higher PD-L1 expression and a stronger predicted response to immunotherapy.
Conclusions:
- Distinct m6A modification patterns in melanoma are associated with differential immune characteristics.
- The developed m6Ascore system can predict patient prognosis and immunogenicity, aiding clinical decision-making and personalized treatment strategies.
