Creating a multifaceted prognostic model for cutaneous melanoma: the convergence of single-cell and bulk sequencing with machine learning.

ABSTRACT

Background: Cutaneous melanoma is a highly heterogeneous cancer, and understanding the role of inflammation-related genes in its progression is crucial. Methods: The cohorts used include the TCGA cohort from TCGA database, and GSE115978, GSE19234, GSE22153 cohort, and GSE65904 cohort from GEO database. Weighted Gene Coexpression Network Analysis (WGCNA) identified key inflammatory modules. Machine learning techniques were employed to construct prognostic models, which were validated across multiple cohorts, including the TCGA cohort, GSE19234, GSE22153, and GSE65904. Immune cell infiltration, tumor mutation load, and immunotherapy response were assessed. The hub gene STAT1 was validated through cellular experiments. Results: Single-cell analysis revealed heterogeneity in inflammation-related genes, with NK cells, T cells, and macrophages showing elevated inflammation-related scores. WGCNA identified a module highly associated with inflammation. Machine learning yielded a CoxBoost + GBM prognostic model. The model effectively stratified patients into high-risk and low-risk groups in multiple cohorts. A nomogram and Receiver Operating Characteristic (ROC) curves confirmed the model's accuracy. Low-risk patients exhibited increased immune cell infiltration, higher Tumor Mutational Burden (TMB), and potentially better immunotherapy response. Cellular experiments validated the functional role of STAT1 in melanoma progression. Conclusion: Inflammation-related genes play a critical role in cutaneous melanoma progression. The developed prognostic model, nomogram, and validation experiments highlight the potential clinical relevance of these genes and provide a basis for further investigation into personalized treatment strategies for melanoma patients.