Construction Of A Prognosis Risk Model For Skin Cutaneous Melanoma Based On Endoplasmic Reticulum Stress-related Genes

Objective:Endoplasmic reticulum stress(ERS)is a state of elevated concentrations of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum in response to genetic factors and environmental stimuli.Several studies have shown that ERS is intimately associated with the mechanisms of progression of various diseases,especially aggressive malignancies recently.Skin cutaneous melanoma(SKCM)is one of the most aggressive cancers,and studies have shown that ERS affects the progression of SKCM by regulating apoptosis and autophagy-related pathways,and the exact mechanism is not yet clear.Currently,tumor prognostic models based on ERS-related gene profiles have been widely investigated for their decent prognostic value.Studies exploring the role of ERS-related genes in the prognosis of SKCM are lacking.The research was carried out to generate a novel prognostic model using ERS-related genes to evaluate the prognosis of patients suffering from melanoma,with the aim of providing a foundation for individualized treatment and prognosis assessment of SKCM patients.Methods:Expression profile datasets and related survival information of SKCM patients were obtained from public databases such as TCGA and GEO databases,and gene expression profile of normal skin tissues were extracted from GTEx database.After the differentially expressed genes were intersected with ERS-related genes,we filtered the ERS-related prognostic target genes through the Lasso and Cox regression analysis,and a SKCM prognostic risk model was constructed based on these genes.The predictive manifestation of the novel constructed signature was estimated utilizing survival analysis and ROC plots.Addtionally,the prognostic power of the novel signature was tested using an external cohort GSE59455.Patients were arranged into high and low risk categories based on ERS risk scores,and differences in functional enrichment of differential genes,tumor microenvironment,and immune infiltration were evaluated in different risk groups.Results:After differential expression analysis,Lasso and Cox regression analysis,we finally screened 13 ERS-related genes for the construction of the SKCM prognostic risk model.Based on the median risk score,patients were categorized into two risk groups.COX regression demonstrated that this risk score feature could be considered as an independent prognostic element.the ROC curves showed that the area under the curve for the TCGA training cohort was 0.714,0.733,0.776 and 0.768 at 3,5,8 and 10 years,respectively,demonstrating the decent predictive power of the model.GO and KEGG enrichment analyses showed that the differential genes were involved in immune response related processes;GSEA gene set enrichment analysis indicated that the low-risk group was more active in immune response related pathways.Tumor microenvironment,immune infiltration analysis showed that the immune scores of tumor tissues were higher in the low-risk group than in the high-risk group,and the infiltration degree of various immune cells and immune pathways were more active than in the high-risk group.Immune checkpoint analysis showed that the expression level of immune checkpoints in tumor tissues were higher in the low-risk group.Conclusion:In this study,a novel prognostic risk model for SKCM based on 13 endoplasmic reticulum stress-related genes was constructed,which has decent predictive ability and could offer a reference basis for individualized treatment,prognostic assessment,and evaluation of the effectiveness of immunotherapy for SKCM.