RASSF5在皮肤黑色素瘤中的调控机制及临床意义  

The regulatory mechanism and clinical significance of RASSF5 in skin melanoma

作　　者：顾达 闫宁 李洋 邱尧 邝靖[1] 郭丹凤[1] 邱晓东[1] 娄焕民[1] Gu Da;Yan Ning;Li Yang;Qiu Yao;Kuang Jing;Guo Danfeng;Qiu Xiaodong;Lou Huanmin(Department of Plastic Surgery,Jinan Central Hospital Affiliated to Shandong First Medical University,Jinan 250013,China)

机构地区：[1]山东第一医科大学附属济南市中心医院整形外科,250013

出　　处：《中华整形外科杂志》2021年第8期863-874,共12页Chinese Journal of Plastic Surgery

摘　　要：目的探讨RASSF5在皮肤黑色素瘤中的调控机制及临床意义。方法使用GEPIA和HPA在线工具以及癌症基因组图谱和GSE53118数据集,进行差异表达分析和预后分析;使用cBioPortal分析RASSF5的表达与基因突变和甲基化之间的相关性;使用limma R包筛选差异基因并进行GO分析、KEGG分析和蛋白相互作用分析,同时对所有基因进行GSEA分析;最后使用ESTIMATE和CIBERSORTx在线工具评估免疫细胞浸润程度。对于计量资料,采用Kruskal test比较各组之间的差异,使用Kaplan-Meier方法绘制生存曲线,使用Cox比例风险回归模型进行单变量和多变量分析。结果研究发现,在皮肤黑色素瘤中,RASSF5的表达水平明显低于正常组织,并且与其甲基化水平存在负相关。KEGG分析及GSEA分析显示RASSF5与免疫调节、KRAS、P53等多种信号通路相关。进一步分析显示,RASSF5的表达水平与多种肿瘤免疫细胞浸润程度呈正相关。生存分析发现RASSF5的表达水平与皮肤黑色素瘤患者的总生存率相关,同时多因素回归分析发现RASSF5是皮肤黑色素瘤的独立预测因子。最后,使用GSE53118数据集再次验证RASSF5与皮肤黑色素瘤患者的总生存率相关,可以作为独立预测因子。结论RASSF5可能通过多种途径调控皮肤黑色素瘤细胞的发生发展,是皮肤黑色素瘤潜在的生物学预后标志物及治疗靶标。Objective To investigate the regulatory mechanism and clinical significance of RASSF5 in cutaneous melanoma.Methods We used GEPIA and HPA online tools and TCGA and GSE53118 data sets for differential expression analysis and prognosis analysis;cBioPortal was applied to analyze the correlation between RASSF5 expression and gene mutation and methylation;"limma"R package was used to screen differential genes for GO analysis,KEGG analysis and protein-protein interaction analysis,and we also performed GSEA analysis on all genes;finally we used ESTIMATE and CIBERSORTx online tools to evaluate immune cell infiltration.The kruskal test was used to compare the differences between the groups for measurement data,the Kaplan-Meier method was used to draw the survival curve,and the Cox proportional hazard regression model was used for univariate and multivariate analysis.Results This study found that in cutaneous melanoma,the expression level of RASSF5 was significantly lower than that of normal tissues,and the methylation level was negatively correlated.KEGG analysis and GSEA analysis showed that RASSF5 can be related to multiple signaling pathways such as immune regulation,KRAS,and P53.Further analysis showed that the expression level of RASSF5 was positively correlated with the degree of infiltration of a variety of tumor immune cells.Survival analysis found that the expression level of RASSF5 was correlated with the overall survival rate of patients with cutaneous melanoma,and multivariate regression analysis found that RASSF5 was an independent predictor of cutaneous melanoma.Finally,using the GSE53118 dataset to verify again,RASSF5 is related to the overall survival rate of patients with cutaneous melanoma and can be used as an independent predictor.Conclusions RASSF5 may regulate the occurrence and development of cutaneous melanoma cells through a variety of ways.It is a potential biological prognostic marker and therapeutic target.

关 键 词：黑色素瘤 预后 免疫调节 计算生物学 RASSF5 

分 类 号：R739.5[医药卫生—肿瘤]