Related Experiment Video
Updated: Oct 7, 2025
DNA-barcode-based Multiplex Immunofluorescence Imaging to Analyze FFPE Specimens from Genetically Reprogrammed Murine Melanoma
Published on: June 6, 2025
Identification of m6A Regulator-Associated Methylation Modification Clusters and Immune Profiles in Melanoma
Fengying Du1,2,3, Han Li4, Yan Li5
1Department of Dermatology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
Abstract:
RNA N6-methyladenosine (m6A) modification in tumorigenesis and progression has been highlighted and discovered in recent years. However, the molecular and clinical implications of m6A modification in melanoma tumor microenvironment (TME) and immune infiltration remain largely unknown. Here, we utilized consensus molecular clustering with nonnegative matrix factorization based on the melanoma transcriptomic profiles of 23 m6A regulators to determine the m6A modification clusters and m6A-related gene signature. Three distinct m6A modification patterns (m6A-C1, C2, and C3), which are characterized by specific m6A regulator expression, survival outcomes, and biological pathways, were identified in more than 1,000 melanoma samples. The immune profile analyses showed that these three m6A modification subtypes were highly consistent with the three known immune phenotypes: immune-desert (C1), immune-excluded (C2), and immune-inflamed (C3). Tumor digital cytometry (CIBERSORT, ssGSEA) algorithm revealed an upregulated infiltration of CD8+ T cell and NK cell in m6A-C3 subtype. An m6A scoring scheme calculated by principal component of m6A signatures stratified melanoma patients into high- and low-m6sig score subgroups; a high score was significantly associated with prolonged survival and enhanced immune infiltration. Furthermore, fewer somatic copy number alternations (SCNA) and PD-L1 expression were found in patients with high m6Sig score. In addition, patients with high m6Sig score demonstrated marked immune responses and durable clinical benefits in two independent immunotherapy cohorts. Overall, this study indicated that m6A modification is involved in melanoma tumor microenvironment immune regulation and contributes to formation of tumor immunogenicity. Comprehensive evaluation of the m6A modification pattern of individual tumors will provide more insights into molecular mechanisms of TME characterization and promote more effective personalized biotherapy strategies.
Insights
RNA N6-methyladenosine (m6A) modification impacts melanoma progression and immune infiltration. Identifying m6A patterns can predict patient survival and guide personalized immunotherapy strategies.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- RNA N6-methyladenosine (m6A) modification plays a role in cancer, but its impact on the melanoma tumor microenvironment (TME) and immune infiltration is unclear.
- Understanding m6A's role is crucial for developing effective melanoma treatments.
Purpose of the Study:
- To investigate the molecular and clinical implications of m6A modification in the melanoma TME.
- To identify m6A-related gene signatures and their association with immune infiltration and patient outcomes.
Main Methods:
- Consensus molecular clustering using nonnegative matrix factorization on melanoma transcriptomic data of 23 m6A regulators.
- Analysis of immune profiles, survival outcomes, and somatic copy number alterations (SCNA).
- Calculation of an m6A scoring scheme and validation in immunotherapy cohorts.
Main Results:
- Three distinct m6A modification patterns (m6A-C1, C2, C3) were identified, correlating with immune phenotypes (desert, excluded, inflamed).
- The m6A-C3 subtype showed increased CD8+ T cell and NK cell infiltration.
- A high m6A score was linked to improved survival, enhanced immune infiltration, fewer SCNA, lower PD-L1 expression, and better response to immunotherapy.
Conclusions:
- m6A modification is integral to melanoma TME immune regulation and tumor immunogenicity.
- m6A patterns can stratify patients and predict immunotherapy response.
- Evaluating m6A modification patterns offers insights for personalized melanoma biotherapy.
