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

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

doi:10.3892/ol.2020.12138

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

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

Authors

Xiangtian Wu¹, Gang Liu², Ruiting Liu¹, Jing He³, Guorong Wang¹, Haibao Zhang⁴, Tianjie Liu⁴, Jirong Bai⁵, Ning Cheng¹, Jian Qiu¹

Affiliations

¹ Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710061, P.R. China.
² Department of Emergency Surgery, East Hospital, Tongji University, Shanghai 200120, P.R. China.
³ Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
⁴ Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710000, P.R. China.
⁵ Department of Pathology, University of Nebraska Medical Center, Omaha, NE 68198, USA.

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 χ² 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.

Keywords: colorectal cancer; prognosis; ubiquitin-conjugating enzyme E2T; ubiquitination.