Integrated Single-Cell and Bulk RNA Sequencing Analysis Identifies a Regulated Cell Death-Related Gene Signature for Predicting Prognosis and Therapeutic Responses in Cutaneous Melanoma

Regulated cell death (RCD) is crucial for the advancement of cancers, and providing opportunities as prognostic indicators and immunotherapy markers for patients with cutaneous melanoma (CM). Ten multiomics integrative clustering approaches were performed to identify the CM subtypes. Subsequently, WGCNA was used to screen for module genes. Furthermore, screening hub genes was conducted through machine-learning analyses. Two CM subclasses were identified based on RCD multiomics profiling, each exhibiting distinctive molecular patterns. Then, utilizing the shared cluster DEGs, prognosis DEGs, and key module genes, 30 hub genes were obtained, and an RCD.score was conducted based on these genes. The RCD.score not only reflected the characteristics of the clinical but also provided insights into immunotherapy efficacy. Specifically, low RCD.score category exhibited a more active TME and favorable prognosis, those in the low RCD.score category was more responsive to immunotherapy, suggesting an inflamed TME phenotype. The high RCD.score category had a poor prognosis and was lower responsive to immunotherapy. This research offers genetic support for the possible therapeutic advantages of focusing on RCD in the treatment of CM while also examining their underlying pathophysiological mechanisms.