Unraveling outcome-related co-expression modules and their impact on the melanoma microenvironment through integration of bulk and single-cell data

Melanoma is an aggressive form of skin cancer with complex immune interactions in the tumor microenvironment (TME). In this study, a comprehensive transcriptional and single-cell RNA sequencing analysis was conducted to identify outcome-related coexpression modules and patient subgroups in melanoma. Two distinct subgroups, S1 (Scissor − ) and S2 (Scissor + ), with significantly different prognostic outcomes, were detected. S1 was linked to immunological activation, whereas S2 was characterized by transcriptional features associated with reduced immune activity. The coexpression analysis revealed 126 outcome-related modules, with immune-related pathways enriched in S1 and tumor progression pathways in S2. Single-cell analysis indicated that S2 contained more stromal components, such as cancer-associated fibroblasts, whereas S1 possessed a higher proportion of immune cells, specifically CD8 + T-cells and macrophages. In addition, functional analysis signified that the TME of S2 cells was more immunosuppressive. In contrast, the S1 group showed a transition from CD8 + Teff to cycling T-cells, implying persistent immunological activation. These findings provide a transcriptomic framework for understanding outcome-associated immune ecosystem states in melanoma and generate hypotheses regarding cellular interactions associated with distinct prognostic phenotypes.