| Background:Melanoma(mm)is a malignant tumor with the highest mortality rate in dermatology.It has the characteristics of rapid progress,easy metastasis and insensitive to radiotherapy and chemotherapy.It seriously threatens people’s health and quality of life.At present,the molecular mechanism of melanoma is not completely clear,and its development has always been the focus of skin tumor research.Studies have shown that oxidative stress is closely related to the occurrence and development of melanoma,which is also one of the hot spots of tumor mechanism research in recent years.Glutathione peroxidases(GPX)is an important antioxidant enzyme in human body.Because it is involved in the occurrence and development of kidney cancer,lung adenocarcinoma,colorectal cancer,skin squamous cell carcinoma and other tumors,it has attracted much attention in the field of oxidative stress and tumor research.At present,no relevant research on GPXs and the occurrence,development and prognosis of melanoma has been retrieved.Objective:The purpose of this study was to explore the relationship between GPXs gene alterations and expression,immune cell infiltration and prognosis of melanoma by means of bioinformatics analysis and the possible main pathways of GPXs regulation in melanoma were also discussed.Methods:1.Analysis of the relationship between gene alterations of GPXs and prognosis of melanomaThe correlation between GPXs expression was analyzed by R language,and then the interaction between GPXs and its most frequently changed adjacent genes was analyzed by Gene MANIA.Enrichr performed go analysis and KEGG pathway enrichment analysis of GPXs gene online,and mapped the major metabolic pathways regulated by GPXs changes using R language.Then the gene alterations of GPX in melanoma patients were observed in c Bioportal,and the correlation between gene alterations and overall survival(OS)of melanoma was analyzed by Kaplan Meier curve.2.Analysis of the relationship between GPXs expression and prognosis of melanomaThe expression level of GPXs m RNA in melanoma and normal samples was determined through Oncomine database and the expression difference of GPXs in different clinical types of melanoma was also explored.The differentially expressed genes were screened,and the GPXs expression was semi quantitatively analyzed in GEPIA and to compare the expression difference between different pathological stages of melanoma.To study the correlation between GPXs expression and prognosis of melanoma by Linked Omics.3.GO analysis of GPXs gene and enrichment analysis of KEGG pathwayEnrichr performed go analysis and KEGG pathway enrichment analysis of GPXs gene online,and mapped the major metabolic pathways regulated by GPXs changes using R language.4.Analysis of the relationship between GPXs expression and melanoma immune cell infiltration and prognosisTIMER online analyzed the relationship between GPXs expression,immune cell infiltration and prognosis in patients with melanoma.5.Statistical methodsThrough Linked Omics,c Bioportal and GEPIA online software obtained HR,log test p value or adjusted p value through log rank test,and generate Kaplan Meier curve.The results of Oncomine and TIMER online software are displayed as p values.Pearson correlation coefficient was used to evaluate the correlation between gene expression.Results:1.Analysis of the relationship between GPXs gene changes and melanoma prognosis(1)there is a very weak to strong correlation between the expression of GPXs genes.The co expression network was constructed and the interaction with the 20 adjacent genes most frequently changed by GPXs was found.(2)The change rates of GPX1,2,3,4,7 and 8 were 4%,10%,4%,6%,5%and 2.8%respectively.(3)Patients with melanoma had shorter OS than those without GPX2gene change(p<0.05).2.Analysis of the relationship between the expression of GPXs and the prognosis of melanoma(1)The expression of GPX1,7 and 8 in melanoma was higher than that in normal tissues,while the expression of GPX2 and 3 was lower than that in normal skin tissues.(2)The expression of GPX2 was significantly different among the pathological stages of cutaneous melanoma(p<0.05),and there was no significant difference in other GPXs(p>0.05).(3)In patients with melanoma,the prognosis of patients with high expression of GPX7 and 8 was worse,while the prognosis of patients with high expression of GPX1 was better(all p<0.05).There was no significant correlation between the expression of other GPXs and the prognosis of melanoma(p>0.05).3.GO analysis of GPXs gene and enrichment analysis of KEGG pathway(1)GO-BP analysis showed that GPXs were mainly enriched in cell response to chemical stress,cell response to oxidative stress and selenocysteine incorporation.GO-CC analysis showed that GPXs were mainly enriched in endoplasmic reticulum cavity,smooth endoplasmic reticulum and sarcoplasmic reticulum.GO-MF analysis showed that GPXs were mainly enriched in lipase inhibitor activity,phospholipase inhibitor activity and NADH dehydrogenase(quinone)activity.(2)KEGG analysis showed that in melanoma,GPXs may play a role by regulating glutathione metabolism,arachidonic acid metabolism,iron death and other pathways.4.Analysis of the relationship between GPXs expression and melanoma immune cell infiltration and prognosis(1)GPX1 expression was positively correlated with dendritic cell infiltration(p<0.05);(2)The expression level of GPX2 was negatively correlated with the infiltration of B cells,CD4~+T cells,macrophages,neutrophils and dendritic cells(all p<0.05);(3)The expression of GPX3 was positively correlated with the infiltration of B cells,CD8~+T cells,macrophages and dendritic cells(all p<0.05);(4)The expression of GPX4 was positively correlated with the infiltration of CD8~+T cells and neutrophils(all p<0.05);(5)There was a significant positive correlation between GPX7expression and immune cell infiltration of B cells,CD4~+T cells,macrophages,neutrophils and dendritic cells(all p<0.05);(6)The expression of GPX8 was positively correlated with the infiltration of CD4~+T cells,macrophages and neutrophils(all p<0.05).(7)The level of dendritic cell infiltration was positively correlated with OS in patients with melanoma(p<0.05,HR=0.132,95%CI=0.057-0.307).Conclusion:1.The prognosis of melanoma patients without GPX2 gene change is better than that of melanoma patients with GPX2 gene change,which is expected to become a potential therapeutic target for melanoma patients.2.The expression of GPX1,7 and 8 is correlated with the prognosis of melanoma,and is expected to be used as a prognostic marker for melanoma patients.3.In melanoma,GPXs may play a role by regulating glutathione metabolism,arachidonic acid metabolism,iron death and other pathways.4.The expression of GPXs in melanoma patients is accompanied by different levels of immune cell infiltration.The level of dendritic cell infiltration is highly correlated with the clinical prognosis of melanoma patients,GPX1,2,3,7 by dendritic cells infiltrating level affects the prognosis of patients with melanoma,which may provide a potential direction for the further study of melanoma immunotherapy. |
