基于TCGA数据乳腺癌组织UBE2T表达临床意义分析

Identification of potential prognostic value of UBE2T expression in breast cancer:a study based on TCGA dataset analysis

目的既往研究发现,泛素结合酶E2T(ubiquitin-conjugating enzyme E2T,UBE2T)在多种肿瘤中表达升高,然而UBE2T在乳腺癌中是否存在高表达及意义尚不清楚。本研究探讨UBE2T表达水平在乳腺癌中的临床意义和可能的机制。方法从癌症基因组图谱(the cancer genome atlas,TCGA)数据库下载正常乳腺组织和乳腺癌组织中UBE2T基因mRNA二代测序数据及临床信息资料,分析UBE2T mRNA表达水平与乳腺癌临床病理学参数的相关性及对预后的影响。采用Cox回归多因素分析探讨影响乳腺癌患者预后的因素,采用基因集富集分析(gene set enrichment analysis,GSEA)方法预测UBE2T可能的调控通路。结果 UBE2T mRNA在乳腺癌组织中表达量为9.28~3 963.54,中位374.18,显著高于正常乳腺组织中UBE2T表达量8.54~216.13,中位40.44,差异有统计学意义(P<0.001),而且UBE2T表达水平与乳腺癌患者年龄、分子分型、T分期、TNM分期、雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)和人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)状态以及病理类型存在显著相关,均P<0.05。进一步分析发现,UBE2T低表达的患者生存预后优于UBE2T高表达的患者,χ~2=7.490,P=0.006。Cox多因素分析结果表明,年龄、分子分型、N分期、M分期和UBE2T表达水平等均是影响乳腺癌患者预后的独立预后因素,P<0.05。GSEA分析表明,UBE2T低表达的组织中存在RIGGINS_TAMOXIFEN_RESISTANCE_DN信号通路(FDR=0.199,P<0.001)和ERB2_UP.V1_DN路通(FDR=0.235,P<0.001)相关基因富集。结论乳腺癌组织中存在UBE2T mRNA水平表达上调,而且UBE2T的表达水平与患者临床病理因素显著相关,其高表达是乳腺癌预后不良因素,其可作为预后判断的分子标记,是潜在的治疗靶点。

OBJECTIVE Studies has indicated that ubiquitin-conjugating enzyme E2T（UBE2T） was up-regulated in several kinds of cancers,however,whether UBE2T is up-regulated in breast cancer has not been reported. Our study was to investigate the potential prognostic value of UBE2T in breast cancer. METHODS The expression data of UBE2T and its clinical information in breast cancer were downloaded from TCGA dataset. Then the relationship between the expres- sion of UBE2T and clinico-pathological characteristics and the prognostic value of UBE2T was analyzed. Cox regression model was performed for the multivariate analysis of the factors affected the prognosis of breast cancer. Gene set enrich- ment analysis（GSEA）was used to predict the regulatory gene sets of UBE2T. RESULTS The expression level of UBE2T mRNA in breast cancer ranged from 9.28 to 3 963.54（median 374.18） ,and was significantly higher than that in normal breast tissues,ranging from 8.54 to 216.13 （median 40.44,P〈0. 001）. Moreover,the expression of UBE2T was signifi- cantly correlated with age, molecular type, T stage, N stage, TNM stage, estrogen receptor （ ER）, progesterone receptor （PR） ,human epidermal growth factor receptor 2 （HER2）and pathological classification, P〈 0. 05. Further analysis showed that low expression of UBE2T indicated a favorable prognosis （χ2 = 7. 490, P= 0. 006）. Multivariate cox regres- sion analysis showed that age,molecular type, T stage,N stage and UBE2T expression were independent prognostic fac- tors of breast cancer patients （P〈.05）. The gene of Tamoxifen-Resistance-DN（FDR= 0. 199, P〈0. 001） and ERB2_UP. VI_DN （FDR = 0. 235, P〈0. 001） were rich in the samples with low expression of UBE2T. CONCLUSIONS UBE2T is significantly upregulated in breast cancer compared with normal breast tissues, moreover, the expression level of UBE2T is correlated with the clinico-pathological characteristics. Up-regulation of UBE2T could be used as a potential poor prognostic maker and therapeutic target in breast cancer.