Objectives: To analyze the expression level of ubiquitin conjugating enzyme E2C (UBE2C) in lung adenocarcinoma and its clinical significance.
Methods: The differences in mRNA and protein expression levels of UBE2C in normal lung tissues and lung adenocarcinoma (LUAD) tissues were determined with the Cancer Genome Atlas (TCGA), Oncomine, and human protein atlas (HPA) databases. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of UBE2C in LUAD. The correlation between UBE2C and LUAD clinicopathological parameters, as well as its relationship with LUAD prognosis was analyzed based on TCGA, International Cancer Genome Consortium (ICGC), and cbioPortal databases. Gene set enrichment analysis (GSEA) was used to analyze the possible pathways of UBE2C in the progression of LUAD.
Results: The mRNA expression level of UBE2C was higher in LUAD tissues than in the normal lung tissues (P<0.01) and it was positively correlated with TNM and N stages (both P<0.05). The UBE2C protein expression level was also increased in LUAD tissues than in the normal lung tissues (P<0.01). ROC curve analysis indicated that UBE2C could be used as an auxiliary diagnostic index for LUAD (AUC=0.969, 95% CI 0.953 to 0.984, P<0.01). Survival analysis showed that the overall survival (OS) of UBE2C high expression group was significantly lower than that of low expression group (P<0.05). The OS of LUAD patients with UBE2C change was lower than that of patients without change (P<0.01). UBE2C was highly expressed in the gene set relevant to cell cycle, p53 signaling pathway, DNA mismatch repair, and DNA replication (all P<0.01).
Conclusions: The expression level of UBE2C is significantly up-regulated in LUAD tissues. The high expression or genetic alteration of UBE2C indicates poor prognosis in LUAD patients. UBE2C can be used as a potential molecular diagnostic marker for LUAD and a potential target for LUAD treatment.
目的: 分析泛素偶联酶E2C(ubiquitin conjugating enzyme E2C，UBE2C)在肺腺癌(lung adenocarcinoma，LUAD)中的表达及其临床意义。方法: 通过癌症和基因肿瘤图谱(the Cancer Genome Atlas，TCGA)数据库、Oncomine数据库、人类蛋白质图谱(human protein atlas，HPA)数据库分析UBE2C在LUAD组织和正常肺组织中mRNA和蛋白质表达水平的差异。采用受试者工作特征(receiver operating characteristic，ROC)曲线分析评估UBE2C诊断LUAD的价值。通过TCGA、国际癌症基因组联盟(International Cancer Genome Consortium，ICGC)数据库、cbioPortal数据库研究UBE2C表达与LUAD患者临床病理特征和预后的关系。通过基因集富集分析(gene set enrichment analysis，GSEA)分析UBE2C参与LUAD发生和发展的可能通路。结果: LUAD组织中UBE2C mRNA表达水平显著高于正常肺组织(P<0.01)，其表达水平与TNM分期、N分期正相关(均P<0.05)；与正常肺组织相比，UBE2C蛋白在LUAD组织中表达水平升高(P<0.01)。ROC曲线分析结果显示：UBE2C诊断LUAD的AUC值为0.969(95% CI：0.953~0.984，P<0.01)。UBE2C的表达水平与TNM分期有关(P<0.05)。UBE2C表达高低与年龄、性别、TNM分期、T分期及N分期有关(均P<0.05)，且UBE2C高表达组病死率较低表达组高(95/247 vs 68/248，P=0.009)。生存分析结果显示：UBE2C高表达组LUAD患者总生存率(overall survival，OS)显著低于低表达组(P<0.05)。发生UBE2C改变的LUAD患者其OS低于未发生改变者(P<0.01)。UBE2C高表达富集在与细胞周期、P53信号通路、DNA错配修复、DNA复制等通路相关的基因集(均P<0.01)。结论: UBE2C在LUAD组织中表达显著上调，其高表达或发生基因改变提示LUAD患者预后差，UBE2C可作为一个潜在的LUAD分子诊断标志物，是LUAD治疗的潜在靶点。.
Keywords: database; gene expression; lung adenocarcinoma; prognosis; ubiquitin conjugating enzyme E2C.