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

作者：Liao, Shian; He, Juliang; Liu, Chong; Zhang, Zide; Liao, Hongyu; Liao, Zuowei; Yu, Chaojie; Guan, Jian; Mo, Hao; Yuan, Zhenchao; Liang, Tuo; Lu, Zhaojun; Xu, Guoyong; Wang, Zequn; Chen, Jiarui; Jiang, Jie; Zhan, Xinli^*

来源：Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries, 2021, 100(22): e26219.

DOI：10.1097/MD.0000000000026219

• autophagy prognostic signature
• IHC
• molecular mechanisms
• nomogram
• SKCM

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.

• 单位
  1; 南方医科大学; 6