摘要
目的 探讨泛素结合酶E2C(UBE2C)在肾透明细胞癌(KIRC)中的表达模式、临床预后价值以及调节KIRC的分子机制。方法 通过肿瘤基因组图谱数据库(TCGA)和人类蛋白质表达图谱数据库(HPA)分析UBE2C基因在KIRC组织和正常组织中的表达差异。结合KIRC患者的临床信息,利用单因素及多因素Cox回归模型分析UBE2C基因在KIRC患者中的预后价值。通过基因富集分析(GSEA)了解UBE2C基因调控KIRC的分子机制。计算KIRC患者中的浸润免疫细胞含量,并评估UBE2C基因表达水平与免疫细胞浸润含量的相关性。结果 KIRC组织中的UBE2C基因和蛋白表达水平均高于正常肾组织(P<0.05)。KIRC组织中UBE2C表达与肿瘤位置、组织学分级、病理分期及TNM分期有关(P<0.05)。单因素及多因素Cox回归分析结果显示,UBE2C可作为预测KIRC患者总生存期(OS)的独立预后因素(P<0.05)。GSEA结果表明,UBE2C可能参与调节细胞因子-细胞因子受体相互作用、细胞周期检查点、ECM糖蛋白等多条信号通路。UBE2C基因表达水平与KIRC肿瘤微环境中Treg细胞、T细胞、Th17细胞、B细胞、CD8+T细胞和巨噬细胞浸润等显著相关。UBE2C同免疫检查点分子PDCD1(PD1)、CTLA4、CD27、LAG3等表达水平也显著相关。结论 UBE2C可作为KIRC患者的一个风险预后因子,同时UBE2C可能作为KIRC治疗的潜在靶点。
Objective To explore the expression pattern, clinical prognostic value and molecular mechanism of ubiquitin-conjugating enzyme E2C(UBE2C) in kidney renal clear cell carcinoma(KIRC). Methods The difference of UBE2C gene expression in KIRC tissue and normal tissue was analyzed by The Cancer Genome Atlas(TCGA) and Human Protein Atlas(HPA). Combined with clinical information of KIRC patients, univariate and multivariate Cox regression analysis models were used to study the prognostic value of UBE2C gene in KIRC patients. Through gene set enrichment analysis(GSEA) of UBE2C gene, we understood the molecular mechanism of UBE2C regulating KIRC. The infiltrating immune cells content in KIRC patients were calculated, and the correlation between UBE2C gene expression level and immune cells infiltration content were evaluated. Results Both gene and protein expression levels of UBE2C in KIRC tissues were higher than those in normal tissues(P<0.05). The expression of UBE2C in KIRC was correlated with tumor location, histological grade, pathological stage and TNM stage(P<0.05). Univariate and multivariate Cox regression analysis cleared that UBE2C was an independent prognostic factor for KIRC(P<0.05). GSEA results suggested that UBE2C could be involved in the regulation of cytokine-cytokine receptor interactions, cell cycle checkpoints, ECM glycoproteins and other signaling pathways. The expression level of UBE2C gene was significantly correlated with the infiltration of Treg cells, T cells, Th17 cells, B cells, CD8+T cells and macrophages in the tumor microenvironment of KIRC. UBE2C was also significantly correlated with the expression levels of immune checkpoint molecules PDCD1(PD1), CTLA4, CD27 and LAG3. Conclusion UBE2C can serve as a risk prognostic factor for KIRC patients, and UBE2C may be a potential target for KIRC treatment.
作者
占天鹏
何魏
张勐
陶燕
卢建中
付生军
李兰兰
张静
刘善辉
ZHAN Tianpeng;HE Wei;ZHANG Meng;TAO Yan;LU Jianzhong;FU Shengjun;LI Lanlan;ZHANG Jing;LIU Shanhui(Second Clinical Medical College of Lanzhou University,Lanzhou 730030,China)
出处
《临床肿瘤学杂志》
CAS
2023年第1期49-57,共9页
Chinese Clinical Oncology
基金
兰州大学第二医院“萃英学子科研培育”计划资助项目(CYXZ2021-22)。
