Construction of autophagy prognostic signature and analysis of prospective molecular mechanisms in skin cutaneous melanoma patients

Abstract

Background: Autophagy is closely related to skin cutaneous melanoma (SKCM), but the mechanism involved is unclear. Therefore, exploration of the role of autophagy-related genes (ARGs) in SKCM is necessary.

Materials and methods: Differential expression autophagy-related genes (DEARGs) were first analysed. Univariate and multivariate Cox regression analyses were used to evaluate the expression of DEARGs and prognosis of SKCM. Further, the expression levels of prognosis-related DEARGs were verified by immunohistochemical (IHC) staining. Finally, gene set enrichment analysis (GSEA) was used to explore the underlying molecular mechanisms of SKCM.

Results: Five ARGs (APOL1, BIRC5, EGFR, TP63, and SPNS1) were positively correlated with the prognosis of SKCM. IHC verified the results of the differential expression of these 5 ARGs in the bioinformatics analysis. According to the receiver operating characteristic curve, the signature had a good performance at predicting overall survival in SKCM. The signature could classify SKCM patients into high-risk or low-risk groups according to distinct overall survival. The nomogram confirmed that the risk score has a particularly large impact on the prognosis of SKCM. Calibration plot displayed excellent agreement between nomogram predictions and actual observations. Principal component analysis indicated that patients in the high-risk group could be distinguished from those in low-risk group. Results of GSEA indicated that the low-risk group is enriched with aggressiveness-related pathways such as phosphatidylinositol-3-kinase/protein kinase B and mitogen-activated protein kinase signalling pathways.

Conclusion: Our study identified a 5-gene signature. It revealed the mechanisms of autophagy that lead to the progression of SKCM and established a prognostic nomogram that can predict overall survival of patients with SKCM. The findings of this study provide novel insights into the relationship between ARGs and prognosis of SKCM.