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Integrating multi-omics data to resolve patterns of ion channel regulation in melanoma and predict tumor treatment
Jiahua Xing1, Muzi Chen2, Ran Tao3
1Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, 100144, China.
Abstract:
Skin cutaneous melanoma (SKCM) represents a highly aggressive malignancy with rising incidence, characterized by early metastatic potential and development of treatment resistance in advanced stages. While ion channel-related genes (ICRGs) demonstrate therapeutic relevance across cancers, their role in SKCM remains incompletely defined. A comprehensive assessment of ICRG regulatory patterns was conducted in SKCM samples using single-cell spatial transcriptomic and multi-omics data. These patterns were correlated with tumor microenvironment (TME) cell infiltration characteristics to construct ICRG scores quantifying tumor-specific ICRG modification patterns. The ICRG.Gene.cluster stratifies samples into two distinct subpopulations representing divergent immune phenotypes. An ICRG scoring system is constructed based on ICRG phenotype genes and validated in independent cohorts. Through ICRG-associated gene profiling, CD8⁺ T cells are categorized into five subsets, all exhibiting significant temporal dynamics in pseudotime analysis. Spatial transcriptomics confirms prominent co-localization spots between the C3 CD8⁺ T cell subset and melanoma cells. SCENIC analysis identifies that specific ICRG genes function as target nodes regulated by transcription factors. Core ICRG genes demonstrate elevated expression in both cell lines and clinical specimens, supporting their potential role as disease-associated genetic risk loci. ICRG modification patterns provide critical insights into TME infiltration heterogeneity, enabling refined prognostic assessment and therapeutic targeting strategies.
Insights
Ion channel-related genes (ICRGs) influence skin cutaneous melanoma (SKCM) progression and immune interactions. Understanding ICRG patterns offers new strategies for SKCM prognosis and targeted therapies.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Skin cutaneous melanoma (SKCM) is an aggressive cancer with increasing incidence and resistance to treatment.
- The role of ion channel-related genes (ICRGs) in SKCM is not fully understood, despite their therapeutic relevance in other cancers.
Purpose of the Study:
- To comprehensively assess ICRG regulatory patterns in SKCM.
- To correlate these patterns with tumor microenvironment (TME) characteristics.
- To develop ICRG-based scores for prognostic and therapeutic insights.
Main Methods:
- Utilized single-cell spatial transcriptomics and multi-omics data from SKCM samples.
- Developed ICRG scores based on tumor-specific modification patterns and TME infiltration.
- Employed SCENIC analysis to identify transcription factor regulation of ICRGs.
- Categorized CD8+ T cell subsets and analyzed their dynamics using pseudotime analysis.
Main Results:
- ICRG patterns stratified SKCM samples into two distinct immune phenotypes.
- An ICRG scoring system was developed and validated in independent cohorts.
- Spatial transcriptomics revealed co-localization of a specific CD8+ T cell subset with melanoma cells.
- Core ICRG genes showed elevated expression, suggesting their role as disease-associated genetic risk loci.
Conclusions:
- ICRG modification patterns provide critical insights into TME heterogeneity in SKCM.
- ICRG scores can refine prognostic assessment and guide therapeutic targeting strategies for SKCM.
- Further investigation into ICRGs may reveal novel therapeutic targets for melanoma.
