Telomere Maintenance Patterns Exhibit Distinct Prognostic and Immune Landscapes in Cutaneous Malignant Melanoma

Abstract Background Cutaneous malignant melanoma (CMM) is notorious for its ability to metastasize or spread to other parts of the body, rendering it one of the most perilous forms of skin cancer. This study aims to investigate the prognostic significance of telomere maintenance in CMM. Materials & Methods A total of 593 CMM samples were collected from TCGA and GEO datasets. CMM samples were clustered into two telomere maintenance clusters using nonnegative matrix factorization (NMF). Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were employed to investigate the biological difference between distinct TM modification patterns. The immune landscape of CMM was visualized through single-sample gene-set enrichment analysis (ssGSEA) and CIBERSORT. Additionally, a risk score was identified using least absolute shrinkage and selection operator (LASSO), and hub-genes were determined via multi-variate COX analysis. Survival analyses were performed using the Kaplan-Meier method, and differences in survival were assessed using the log-rank test. Single-cell sequencing validation was conducted using the Tumor Immune Single Cell Hub on GSE123139 dataset(TISCH). Results Two telomere maintenance patterns were identified based on CMM samples. There were 6 hub-genes were screened by LASSO and multi-variate COX analyses and risk score was calculated based on the expression and coefficient of each hub-gene. CMM samples were classified into low- and high-risk groups. The overall survival (OS) of low-risk group was significantly higher than the high-risk group. A prognostic signature was identified based on risk score and patients’ clinical characteristics and visualized by nomogram. Conclusions Our study explored the potential prognostic value of telomere maintenance in CMM. We have developed a prognostic signature for CMM based on telomere maintenance related genes. telomere maintenance may aid in risk stratification and treatment strategy for patients with CMM.