DLGAP5基因突变与甲基化在肾透明细胞癌中的预后及意义  

Prognosis of DLGAP5 in kidney renal clear cell carcinoma

作　　者：孙井涛 郭长春[2] 许传兵[3] 井学辉 张鸿志 王乃强 李大伟[1] 阎磊[1] Sun Jingtao;Guo Changchun;Xu Chuanbing;Jing Xuehui;Zhang Hongzhi;Wang Naiqiang;Li Dawei;Yan Lei(Qilu Hospital of Shandong University,Jinan 250012,China;Huangdao District Peoples Hospital,Qingdao 266400,Shandong,China;Zibo Central Hospital,Zibo 255000,Shandong,China;Yucheng People’s Hospital,Dezhou 251200,Shandong,China)

机构地区：[1]山东大学齐鲁医院泌尿外科,济南250012 [2]山东省青岛市黄岛区人民医院泌尿外科,山东青岛266400 [3]淄博市中心医院泌尿外科,山东德州251200 [4]山东省禹城市人民医院泌尿外科,济南250012

出　　处：《泌尿外科杂志（电子版）》2022年第2期31-38,共8页Journal of Urology for Clinicians(Electronic Version)

基　　金：山东省重点研发计划(2019GSF108255)。

摘　　要：目的探讨DLGAP5(discs large homolog associated protein 5)基因在肾透明细胞癌(kidney renal clear cell carcinoma,KIRC)患者中的表达水平、与T细胞免疫的关系、相关临床预后意义、基因突变水平以及甲基化程度(表观遗传学方面),以提供一种更新的肾透明细胞癌的早期诊断方法及相应治疗方案。方法通过在UCSC Xena数据库下载并分析KIRC相关基因表达样本数据共607例,其中,正常样本72例,肿瘤样本535例,且所有样本表达DLGAP5基因。明确DLGAP5基因在肾透明细胞癌组织与正常肾组织之间的表达差异,探究肾透明细胞癌患者DLGAP5基因表达与T淋巴细胞和T细胞表达基因之间的相关性,研讨DLGAP5基因突变水平以及甲基化水平,探讨DLGAP5基因对于肾透明细胞癌预后的预测能力。结果DLGAP5基因在肾透明细胞癌细胞中的表达水平明显高于其在正常肾脏组织中的表达水平;DLGAP5低表达组(n=266)总生存数明显优于DLGAP5基因高表达组(n=265)的患者(P=0.001),尤以明确KIRC诊断后的第1年变化程度最为明显,其中,DLGAP高表达组死亡51人,而DLGAP5低表达组仅死亡40人。12年后,DLGAP5高表达组患者全部死亡,而DLGAP5低表达组中仍有1人存活;DLGAP5基因在经过单因素独立预后分析(P<0.001)和多因素独立预后分析(P=0.001)后,可确定为肾透明细胞癌的高风险独立预后因子;DLGAP5基因表达量与CD8~+T细胞含量(Rho=0.298,P<0.001)、CD2免疫基因表达量(Rho=0.393,P<0.001)、CD3D免疫基因表达量(Rho=0.354,P<0.001)呈正相关关系以及CD3E免疫基因表达量(Rho=0.353,P<0.001)呈正相关;DLGAP5的基因突变水平无法作为患者预后的诊断指标;cg10130446甲基化位点的甲基化程度与患者预后呈负相关(P=0.006),DLGAP5的cg10130446甲基化位点可作为患者预后判断的生物学指标和新的治疗靶点。结论DLGAP5基因在肾透明细胞癌细胞中的表达水平明显高于其在正常肾脏组织中的表达水平;DLGAP5�Objective To explore the prognostic relevance of DLGAP5 for patients with kidney renal clear cell carcinoma(KIRC)and the value for the early diagnosis of and target therapy for KIRC.Methods KIRC gene expression data for 607 patients from UCSU Xena were analyzed.Among them,72 cases had normal kidney tissue,and 535 cases had KIRC.The differences in DLGAP5 expression between KIRC and normal kidney tissues were compared,followed by a comparison of correlation between DLGAP5 and immunity.DLGAP5 gene mutation levelwas analyzed using cbioportal plat.The relationship between DLGAP5 methylation levels was evaluated utilizing R software.Results DLGAP5 was significantly increased in KIRC compared to normal kidney tissue.The overall survival in the group with high DLGAP5 expression(n=265)was higher(P=0.001)than that in the group with low DLGAP5 expression(n=266),especially in the first year after diagnosis with KIRC.A total of 51 patients with high DLGAP5 expression died,while only 40 patients with low DLGAP5 expression did.After12 years,all patients in the high DLGAP5 expression group were dead,and one person in the low DLGAP5 expression group was alive.The DLGAP5 gene was identified as a high-risk independent prognostic factor of KIRC after univariate(P<0.001)and multivariate(P=0.001)independent prognostic analyses.The progression-free survival was higher in the low DLGAP5 expression group than in the high DLGAP5 expression group.DLGAP5 gene expression was positively correlated with CD8+T cell content(Rho=0.298,P<0.001),CD2 immune gene expression(Rho=0.393,P<0.001),and CD3 D immune gene expression(Rho=0.354,P<0.001).There was no statistical significance between the level of DLGAP5 mutation and prognosis.Cg10130446,the product of DLGAP5 methylation,was significantly correlated with patient survival(P=0.006).Conclusion DLGAP5 is associated with poor prognosis in patients with renal clear cell carcinoma.The survival rate in the high DLGAP5 expression group was higher than that in the low DLGAP5 expression group.The DLGAP5 gen

关 键 词：肾透明细胞癌 DLGAP5基因 预后 

分 类 号：R737.11[医药卫生—肿瘤]