Survival expectations in melanoma patients: a molecular prognostic model associated with aging

黑色素瘤患者的生存预期:与衰老相关的分子预后模型

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Abstract

BACKGROUND: Aging and long non-coding RNAs (lncRNAs) are research hotspots in melanoma. However, no study has so far explored the relationship between melanoma prognosis and aging-related lncRNAs (ARLs). METHODS: The Cancer Genome Atlas database, the GTEx database, and the HAGR database were used in this study in a combined manner. Univariate and multivariate cox regression analyses were used to screen out lncRNA signatures associated with overall survival (OS) in the primary dataset. The risk scoring model was analyzed by risk stratification and tested internally. The protein expression levels of possible target genes of ARLs were verified by immunohistochemistry analysis in HPA database. Finally, gene enrichment analysis was performed. RESULTS: In the primary dataset, five OS-related lncRNA signatures (AC011481.1, USP30-AS1, EBLN3P, LINC01527, HLA-DQB1-AS1) were screened out. The survival curve showed that the high-risk group had a worse prognosis than the low-risk group. The immunohistochemical analysis revealed that reduced expression of Epidermal Growth Factor Receptor (EGFR), along with increased expression of Activating Transcription Factor 2 (ATF2) and DNA Polymerase Delta 1 (POLD1), was linked to a worse prognosis. Finally, enrichment analysis revealed that OS-related DELs were significantly enriched in the regulation of reactive oxygen metabolism, etc. The ARGs were significantly activated in the SKCM tissues. The regulation of aging in melanoma cells may be realized through ferroptosis, immunity, and autophagy and so on. CONCLUSION: The ARL signature obtained in this study had better prognostic ability than individual clinical features.

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