Bioinformatics Analysis of Prognostic Value and Immune Cell Infiltration of Gene in Cutaneous Melanoma
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Background: Cutaneous melanoma (CM) has a poor overall prognosis. Immune checkpoint inhibitor (ICI) therapy effectively improves overall survival in individuals with advanced melanoma, but only some patients benefit. Serpin Family A Member 1 (), a type of proteinase inhibitor that is used for many targets, is abnormally expressed and plays a vital role in multiple cancers. However, little is known about the clinical significance of in CM.
Methods: The Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) datasets were used to compare expression levels. The association between and other clinical factors were examined with R software, and receiver operating characteristic (ROC) curves for identification was developed. The Tumor IMmune Estimation Resource (TIMER) was used to examine the invasion of immune cells, markers for immune cells, and immunological checkpoints. The predictive value of DNA methylation levels for every CpG was analyzed with the MethSurv web tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to assess the roles of genes that interacted with . The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict 's response to ICIs.
Results: was substantially expressed in CM. Overexpression of was significantly associated with CM severity. The outcome for individuals with elevated expression was good (HR =0.54, P<0.001). Using expression levels, tumors and normal tissues could be reliably differentiated [area under the curve (AUC) =0.889]. Positive associations were found between in CM and the infiltration of immune cells and immunological checkpoints [programmed cell death-1 (PD-1) and CTLA-4]. The efficacy of immune checkpoint blockade (ICB) in patients with a low expression of was good. The GO pathway enrichment analysis showed that activation of neutrophil granulocytes participated in enrichment in the immune response pathway. Patients with low expression had low TIDE scores.
Conclusions: is involved not only in the development and progression of CM but also in the immunological control of CM. Thus, may serve as a possible biomarker for CM diagnosis, as well as its therapeutic target.
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