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泛素结合酶E2T在结直肠癌中的表达及临床意义。

Expression of ubiquitin-conjugating enzyme E2T in colorectal cancers and clinical implications.

作者信息

Wu Xiangtian, Liu Gang, Liu Ruiting, He Jing, Wang Guorong, Zhang Haibao, Liu Tianjie, Bai Jirong, Cheng Ning, Qiu Jian

机构信息

Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710061, P.R. China.

Department of Emergency Surgery, East Hospital, Tongji University, Shanghai 200120, P.R. China.

出版信息

Oncol Lett. 2020 Nov;20(5):275. doi: 10.3892/ol.2020.12138. Epub 2020 Sep 21.

Abstract

Ubiquitin-conjugating enzyme E2T (UBE2T) plays a significant role in carcinogenesis. Previous studies have demonstrated that UBE2T promotes the development and progression of numerous types of cancer. However, the association between UBE2T expression and colorectal cancer (CRC) remains unclear. In the present study, UBE2T protein expression was examined in the tissues of patients with CRC via immunohistochemistry. In addition, UBE2T expression data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA). In the clinical samples, the associations between UBE2T expression and clinicopathological factors were evaluated by the χ or Fisher's exact tests. In TCGA data, associations between UBE2T expression and clinical characteristics were evaluated using a logistic regression model. Overall survival was analyzed using Kaplan-Meier and Cox regression analyses. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting assays were used to examine UBE2T expression in normal and CRC cell lines. Gene set enrichment analysis (GSEA) was performed on the dataset from TCGA. UBE2T protein was highly expressed in the cytoplasm of tumor cells in 29/50 clinical samples, whereas in the adjacent normal tissues, it was only highly expressed in 2/50 samples. Furthermore, UBE2T expression was associated with the N classification (P<0.001), clinical TNM stage (P<0.001) and histological grade of tumors (P=0.010). Survival analysis showed an association between high UBE2T expression and poor survival rate in patients with CRC (P=0.002). Cox regression analysis also revealed that UBE2T expression was an independent prognostic factor for these patients (P=0.006). RT-qPCR and western blotting showed that UBE2T was expressed in CRC cell lines at higher levels than that in a normal colon cell line. Analysis of TCGA data revealed that UBE2T was highly expressed in tumor samples compared with normal samples, but was not associated with prognosis. GSEA showed that high expression of UBE2T was associated with the Kyoto Encyclopedia of Genes and Genomes pathways 'cell cycle', 'oxidative phosphorylation', 'DNA replication', 'p53 signaling pathway', 'ubiquitin mediated proteolysis' and 'pentose phosphate pathway'. These results indicate that UBE2T may play an important role in the progression of CRC and serve as a potential prognostic factor during the treatment of cancer.

摘要

泛素结合酶E2T(UBE2T)在肿瘤发生过程中发挥着重要作用。先前的研究表明,UBE2T促进多种类型癌症的发展和进展。然而,UBE2T表达与结直肠癌(CRC)之间的关联仍不清楚。在本研究中,通过免疫组织化学检测了CRC患者组织中UBE2T蛋白的表达。此外,从癌症基因组图谱(TCGA)获得了UBE2T表达数据及相应的临床信息。在临床样本中,通过χ检验或Fisher精确检验评估UBE2T表达与临床病理因素之间的关联。在TCGA数据中,使用逻辑回归模型评估UBE2T表达与临床特征之间的关联。采用Kaplan-Meier法和Cox回归分析进行总生存分析。使用逆转录定量PCR(RT-qPCR)和蛋白质印迹法检测正常和CRC细胞系中UBE2T的表达。对来自TCGA的数据集进行基因集富集分析(GSEA)。在50份临床样本中的29份中,UBE2T蛋白在肿瘤细胞的细胞质中高表达,而在相邻的正常组织中,仅在50份样本中的2份中高表达。此外,UBE2T表达与N分类(P<0.001)、临床TNM分期(P<0.001)和肿瘤组织学分级(P=0.010)相关。生存分析显示,CRC患者中UBE2T高表达与低生存率相关(P=0.002)。Cox回归分析还显示,UBE2T表达是这些患者的独立预后因素(P=0.006)。RT-qPCR和蛋白质印迹法显示,UBE2T在CRC细胞系中的表达水平高于正常结肠细胞系。对TCGA数据的分析显示,与正常样本相比,UBE2T在肿瘤样本中高表达,但与预后无关。GSEA显示,UBE2T的高表达与京都基因与基因组百科全书途径“细胞周期”、“氧化磷酸化”、“DNA复制”、“p53信号通路”、“泛素介导的蛋白水解”和“磷酸戊糖途径”相关。这些结果表明,UBE2T可能在CRC进展中起重要作用,并可作为癌症治疗期间的潜在预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a46/7520753/c10cdba68afc/ol-20-05-12138-g00.jpg

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