Prognostic score model-based signature genes for predicting the prognosis of metastatic skin cutaneous melanoma.

Purpose: Cutaneous melanoma (SKCM) is the most invasive malignancy of skin cancer. Metastasis to distant lymph nodes or other system is an indicator of poor prognosis in melanoma patients. The aim of this study was to identify reliable prognostic biomarkers for SKCMs.

Methods: Four RNA-sequencing datasets associated with SKCMs were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database as well as corresponding clinical information. Differentially expressed genes (DEGs) were screened between primary and metastatic samples by using MetaDE tool. Weighted gene co-expression network analysis (WGCNA) was conducted to screen functional modules. A prognostic score (PS)-based predictive model and nomogram model were constructed to identify signature genes and independent clinicopathologic factors.

Results: Based on MetaDE analysis and WGCNA, a total of 456 overlapped genes were identified as hub genes related to SKCMs progression. Functional enrichment analysis revealed these genes were mainly involved in the hippo signaling pathway, signaling pathways regulating pluripotency of stem cells, pathways in cancer. In addition, eight optimal DEGs (RFPL1S, CTSV, EGLN3, etc.) were identified as signature genes by using PS model. Cox regression analysis revealed that pathologic stage T, N and recurrence were independent prognostic factors. Three clinical factors and PS status were incorporated to construct a nomogram predictive model for estimating the three years and five-year survival probability of individuals.

Conclusions: The prognosis prediction model of this study may provide a promising method for decision making in clinic and prognosis predicting of SKCM patients.