Expression and clinical significance of SEPHS2 in cutaneous malignant melanoma
Journal Title: Journal of Air Force Medical University - Year 2023, Vol 44, Issue 7
Abstract
Objective To explore the expression and clinical significance of selenophosphoric synthetase 2 (SEPHS2) in cutaneous malignant melanoma (CMM) by bioinformatics methods. Methods The mRNA microarray expression profiles related to CMM and normal skin were downloaded from TCGA and GTEx databases to compare the difference of SEPHS2 gene expression between CMM and normal skin. The GEO dataset GSE3189 was downloaded to compare the difference of SEPHS2 expression between CMM and nevus cells. At the same time, HPA database information was used to analyze its protein expression in CMM and normal melanocytes. The survival difference of CMM patients in different SEPHS2 expression groups was compared by K-M diagram, and HR value was calculated by Cox regression. Receiver operating characteristic curve was used to evaluate the diagnostic efficacy of SEPHS2 in CMM. XENA. UCSC database was used to analyze the methylation of SEPHS2 gene in CMM, and K-M diagram was used to evaluate the impact of different methylation levels of SEPHS2 on prognosis. GSVA package was used to analyze the correlation between SEPHS2 expression and immune cells related to immune infiltration, and STRING database was used to analyze the protein-protein interaction network information related to SEPHS2. GO, KEGG databases and GSEA software were used to explore the function and signal pathway of SEPHS2 in CMM. Results The mRNA expression level of SEPHS2 in CMM was significantly higher than that in normal skin tissue and nevus cell tissue ( P < 0. 001). The CMM patients with high expression of SEPHS2 were found to have a lower overall survival rate than those with low expression, suggesting that SEPHS2 is a promising prognostic marker, which had a good diagnostic value for CMM (AUC = 0. 895, 95% CI: 0. 876 0. 913). Compared with SEPHS2 gene hypermethylation group, hypomethylation group was associated with poor prognosis of CMM, with statistical significance ( P = 0. 013). The expression of SEPHS2 in CMM was negatively correlated with the infiltration of dendritic cells, natural killer cells, T cells, B cells, and cytotoxic cells, and positively correlated with the infiltration of immune cells such as helper T cells, with statistical significance ( P < 0. 05 ) . Protein-protein interaction analysis showed that SEPHS2 interacted with SEPSEC, SCLY, TXNRD1, TXNRD2 and SELK. Enrichment analysis of GO, KEGG and GSEA pathways showed that SEPHS2 and its related genes were involved in and negatively correlated with epidermal formation, humoral immunity, neutrophil activation and immune response, keratin filament and desmosome composition, IL-2, IL-2 family, IL-4-2, IL-10, IL-12-2 and IL-12-STAT4, IL-17, IL-18, IL-27, B cell receptor, T cell receptor, PD-1, CTLA-4 and other immune-related signal pathways. Conclusion SEPHS2 is highly expressed in CMM tissues and is a potential marker for the diagnosis and prognosis of CMM. SEPHS2 is not only involved in the synthesis of selenoproteins, but also affects the immune regulation process of tumors, which may become one of the therapeutic targets of CMM.
Authors and Affiliations
WANG Xudong, XU Jianhong, LI Zhiyong, WANG Jun, HUANG Wei, WANG Lingzhi, LI Chengxin
Keywords
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