Neutrophil extracellular trap related risk score exhibits crucial prognostic value in skin cutaneous melanoma, associating with distinct immune characteristics

Abstract Background Neutrophil extracellular traps (NETs) are related to the prognosis of cancer patients. Nevertheless, the potential prognostic values of NETs in skin cutaneous melanoma (SKCM) remains largely unknown. Materials and methods The NET‐related gene signature was constructed by LASSO Cox regression analysis using the TCGA‐SKCM cohort. The overall survival (OS) and immune status in SKCM patients between the high‐ and low‐NET score (high‐score, low‐score) groups were explored. The scRNA‐seq dataset GSE115978 was used to understand the role of NET score in SKCM at single cell resolution. Results A five NET genes‐based signature (TLR2, CLEC6A, PDE4B, SLC22A4 and CYP4F3) was constructed as the NET‐related prognostic model for SKCM. The OS of SKCM patients with low‐score was better than that in patients with high‐score. Additionally, NET score was negatively associated with infiltration of some immune cells (e.g. type I Macrophages, CD8‐T cells, CD4‐T cells). Moreover, patients with high‐score had low stromal, immune and ESTIMATE scores. Furthermore, drug sensitivity analysis results showed that Lapatinib, Trametinib and Erlotinib may have better therapeutic advantages in patients with high‐score. Conclusion We established a NET‐related five gene signature in SKCM and found that the NET‐related signature may exhibit a good predictive ability for SKCM prognosis. The NET score may not only predict the survival outcome and drug sensitivity in SKCM, but also reflect the immune conditions of SKCM patients.