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.