泛素特异性蛋白酶7基因的泛癌分析及其在瘢痕溃疡癌变中的表达  

Pan-cancer analysis of ubiquitin-specific protease 7 and its expression changes in the carcinogenesis of scar ulcer

作　　者：章思语 阮晶晶[1] 金冬梅 陈诺 谢卫国[1] 阮琼芳[1] Zhang Siyu;Ruan Jingjing;Jin Dongmei;Chen Nuo;Xie Weiguo;Ruan Qiongfang(Institute of Burns,Tongren Hospital of Wuhan University&Wuhan Third Hospital,Wuhan 430060,China;Department of Pathology,Tongren Hospital of Wuhan University&Wuhan Third Hospital,Wuhan 430060,China)

机构地区：[1]武汉大学附属同仁医院暨武汉市第三医院烧伤研究所,武汉430060 [2]武汉大学附属同仁医院暨武汉市第三医院病理科,武汉430060

出　　处：《中华烧伤与创面修复杂志》2023年第6期518-526,共9页Chinese Journal of Burns And Wounds

基　　金：湖北省自然科学基金(2021CFB532);湖北省卫健委科研项目(WJ2021M260);王正国创伤医学发展基金会生长因子复兴计划(SZYZ-TR-10)。

摘　　要：目的探讨泛素特异性蛋白酶7(USP7)在瘢痕溃疡癌变过程中的生物学作用及其临床意义。方法采用回顾性观察性研究结合生物信息学分析方法。从癌症基因组图谱(TCGA)数据库和基因表达综合数据库中获取USP7在肿瘤和/或其对应癌旁正常组织中的RNA表达谱数据,并将RNA测序数据进行log2转化。通过多维度癌症基因集cBioPortal数据库分析USP7基因变异情况,并分析其突变位点。通过TIMER 2.0数据库中“差异表达”模块获得TCGA数据库中肿瘤、癌旁正常组织USP7 mRNA表达情况。使用基因表达谱交互分析2(GEPIA2)数据库分析皮肤黑色素瘤(SKCM)、宫颈鳞状细胞癌(CESC)、肺鳞状细胞癌(LUSC)和头颈鳞状细胞癌(HNSC)中高表达USP7患者与低表达USP7患者的生存率并绘制Kaplan-Meier生存曲线。利用Sangerbox数据库分析USP7在泛癌中的表达与微卫星不稳定性(MSI)或肿瘤突变负担(TMB)的相关性。通过GEPIA2数据库中“相关性分析”模块,评估USP7在泛癌中的表达与5种DNA错配修复基因(MLH1、MSH2、MSH6、PMS2和EPCAM)表达水平和3种必需DNA甲基转移酶(DNMT)——DNMT1、DNMT3A、DNMT3B表达水平的相关性。通过TIMER 2.0数据库中“免疫-基因”模块分析USP7在CESC、HNSC、LUSC和SKCM中表达及其与免疫细胞(B细胞、CD4+T细胞、CD8+T细胞、中性粒细胞、巨噬细胞和树突状细胞)浸润的相关性。利用GEPIA2数据库的“相似基因检测”模块获得与USP7表达模式相似且排名前100的蛋白集。将前述蛋白集与利用STRING数据库获得的与USP7有直接物理结合作用且排名前50的蛋白集进行交集分析。通过DAVID数据库对上述2个蛋白集进行京都基因与基因组百科全书(KEGG)和基因本体论(GO)富集分析。收集2018年10月—2022年10月武汉大学附属同仁医院暨武汉市第三医院病理科有相应临床病理特征的正常皮肤、增生性瘢痕、瘢痕溃疡、瘢痕癌的术后标本,采用�Objective To explore the biological role and clinical significance of ubiquitin-specific protease 7(USP7)in the carcinogenesis of scar ulcer.Methods A retrospective observational study combined with bioinformatics analysis was used.The RNA expression profile data of USP7 in tumor and/or its corresponding paracancular normal tissue were obtained from The Cancer Genome Atlas(TCGA)database and the Gene Expression Omnibus database,and the RNA sequencing data were transformed by log2.The variations of USP7 gene were analyzed by cBioPortal database.The USP7 mRNA expression in tumor and adjacent normal tissue in TCGA database were obtained by using the"Gene_DE"module in TIMER 2.0 database.The survival rates of patients with high and low USP7 expression in cutaneous melanoma(SKCM),cervical squamous cell carcinoma(CESC),lung squamous cell carcinoma(LUSC),and head and neck squamous cell carcinoma(HNSC)were analyzed using the Gene Expression Profile Interactive Analysis 2(GEPIA2)database,and the Kaplan-Meier survival curves were drawn.Sangerbox database was used to analyze the correlation of USP7 expression in pan-cancer with microsatellite instability(MSI)or tumor mutation burden(TMB)pan-cancer.Through the"correlation analysis"module in the GEPIA2 database,the correlation of USP7 expression in pan-cancer with the expression levels of five DNA mismatch repair genes(MLH1,MSH2,MSH6,PMS2,and EPCAM)and three essential DNA methyltransferases(DNMT)--DNMT1,DNMT3A,and DNMT3B were evaluated.The USP7 expression in CESC,HNSC,LUSC,and SKCM and its correlation with infiltration of immune cells(B cells,CD4+T cells,CD8+T cells,neutrophils,macrophages,and dendritic cells)were analyzed by the"Immune-Gene"module in TIMER 2.0 database.The"Similar Genes Detection"module of GEPIA2 database was used to obtain the top 100 protein sets with similar expression patterns to USP7.Intersection analysis was performed between the aforementioned protein sets and the top 50 protein sets that were directly physically bound to USP7 obtained by using the STRI

关 键 词：皮肤肿瘤 瘢痕 泛素特异性蛋白酶7 泛癌分析 瘢痕溃疡 瘢痕癌 创面修复 

分 类 号：R739.5[医药卫生—肿瘤]