关键词: 皮肤黑色素瘤, 染色质重塑, 预后基因, 免疫细胞浸润

Abstract: Objective This study aimed to investigate the association between chromatin remodeling-related genes(CRRGs)and overall survival(OS)of patients with skin cutaneous melanoma(SKCM),and to construct a risk score prognostic prediction model. Methods Based on the TCGA and GTEx databases,the differentially expressed CRRGs in SKCM were obtained,and the prognosis-related genes of SKCM were further screened by protein-protein interaction(PPI)network analysis,univariate Cox regression analysis,and LASSO regression analysis.A risk score prognostic model was constructed based on the prognosis-related genes.According to the median of the risk score,SKCM patients were divided into the high-risk and low-risk groups.The single sample gene set enrichment analysis(ssGSEA)algorithm was used to evaluate the immune cell infiltration of SKCM patients between the high-and low-risk groups. Results A total of 15 hub genes were screened out through the PPI network analysis.Univariate Cox regression and LASSO regression analysis screened out 5 CRRGs associated with OS in SKCM patients,namely MMP2,MMP9,SPP1,TNFSF11,and TIMP1.A risk score was constructed based on the 5 prognostic genes,and multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for SKCM patients(P＜0.05).Survival analysis showed that SKCM patients in the high-risk group was shorter than that in the low-risk group(P＜0.05).The results of immune cell infiltration analysis showed that there were significant differences in the infiltration ratios of 16 immune cells between the high-and low-risk groups,among which the proportions of activated B cells,immature B cells,effector and memory CD8+T cells and activated CD8+T cells in the high-risk group were significantly reduced(P＜0.05).The proportion of CD56bright natural killer cells,CD56dim natural killer cells,γδT cells and immature dendritic cells in the high-risk group were significantly increased(P＜0.05).The drug sensitivity analysis showed that there were significant differences in the sensitivity of high-risk and low-risk SKCM patients to crizotinib,erlotinib,gefitinib and vinorelbine(P＜0.01). Conclusions This study constructed a prognosis model of SKCM composed of 5 CRRGs,further revealed the differences in the immune microenvironment and drug sensitivity in patients with different risk groups of SKCM,and provided an important reference for personalized treatment of SKCM patients.

Key words: Skin cutaneous melanoma, Chromatin remodeling-related genes, Prognostic genes, Immune cell infiltration