Necroptosis-associated classification combined with tumor microenvironment characteristic analysis of cutaneous melanoma

Abstract

Necroptosis is a mode of programmed cell death that overcomes apoptotic resistance. The accurate prognosis of cutaneous melanoma is complicated to predict due to tumor heterogeneity. Necroptosis contributes to the regulation of oncogenesis and cancer immunity. We comprehensively investigated different necroptosis patterns by the non-negative matrix factorization (NMF) clustering analysis and explored the relationships among necroptosis patterns, infiltered immune cells, and tumor microenvironment (TME) scores. Two different necroptosis patterns were identified, and the two clusters could predict prognosis and immune landscape. A four-gene signature was successfully constructed and validated its predictive capability of overall survival (OS) in cutaneous melanoma patients. The prognostic value of the signature was further enhanced by incorporating other independent prognostic factors such as age and clinicopathological stages in a nomogram-based prediction model. Patients with lower risk scores tended to have better OS, higher TME score, immune checkpoints, immunophenoscore (IPS), and lower Tumor Immune Dysfunction and Exclusion (TIDE), which indicated better responses to immunotherapy. In addition, the pigmentation score of the high-risk group was visibly higher than those of the low-risk group. In conclusion, the necroptosis-related signature indicated favorable predictive performance in cutaneous melanoma patients, which provides guidance for immunotherapy and provide novel insights into precision medicine.