In this study, we conducted a comprehensive and detailed assessment of UBE2T expression in ovarian cancer based on online database and to explore its association with clinicopathologic characteristics, survival, function, immune infiltrates and expression difference. Knowing whether a more highly-expression biomarkers in tumor consists of a right away link to ovarian cancer help us understand the mechanistic clarification for observed clinical survival patterns. In our outcomes, UBE2T significantly expression between normal and tumor samples indicated that UBE2T may plays an important role in regulate cancer progression.
UBE2T as for a member of E2 the family in the ubiquitin-proteasome pathway, a complex protein degradation system that participated in extensive biological processes, including signal transduction, tumorigenesis, cell proliferation, differentiation and cell cycle control. Numerous studies identified that its overexpression results in a variety of tumorigenesis such as osteosarcoma, diffuse large B-cell lymphoma and malignant pleural mesothelioma22 − 24. Until now, the expression of UBE2T and its potential prognostic effect on OC has not yet been investigated. Our outcomes showed that OC with UBE2T -high had a more terrible prognosis than that with UBE2T -low (P < 0.05) in OS, PFS and PPS. Moreover, we used UALCAN database to further analysis of multiple clinic pathological features of OC samples and all indicated high transcription of UBE2T. In order to recognize signaling pathways that are differentially in OC, we then performed GSEA analysis among low and high UBE2T expression data sets. The results show that cell cycle, DNA replication, RNA degradation, some cancers, spliceosome, Huntington’s disease, oxidative phosphorylation are differentially enriched in UBE2T high expression phenotype. UBE2T may affect cell cycle, DNA replication, RNA degradation then regulates the occurrence and development of cancer cells. Hao et al25 was first to investigate the expression of UBE2T mRNA in normal human tissues and 8 lung cancer cell lines and found UBE2T was significantly upregulated in lung cancer tissue and cell lines, suggesting involvement of UBE2T in the malignant cell phenotype. The ubiquitin-proteasome system exerts a crucial role in extensive biological processes, and UBE2T, its crucial member, may affect tumorigenesis and cell cycle. Studies on the function of UBE2T in cancer will undoubtedly provide new insights regarding the role UBE2T in both cell cycle regulation and tumorigenesis.
In order to decide the biological interaction network of UBE2T in OC, we applied to tab Network in cBioPortal and the 50 most as often altered neighbor genes of CENPM and the most frequent alterations were HES1. Hes family bHLH transcription factor 1 (HES1) belongs to the basic helix-loop-helix family of transcription factors. A recent study found that Hes1 expression oscillates and drives cyclic expression of the proneural gene Ascl1, which activates cell proliferation in active neural stem cells26. Study also found that indicating that the Notch1/Hes1/MMPs pathway ST6Gal-can mediate the invasiveness and tumorigenicity of non-small cell lung cancer (NSCLC) cells in vitro and in vivo27. Huang et al28 demonstrated that HES1 is a specific downstream gene of NOTCH1 and that it contributes to salivary adenoid cystic carcinoma proliferation, apoptosis and metastasis. In addition, Islam et al reported29 that cisplatin/eugenol sequential combination could be of great therapeutic value for ovarian cancer patients through targeting the Notch-Hes1 pathway and the consequent elimination of the resistant cancer stem cells. So, our study may provide information for HES1 on replication forks study in OC patients.
Until now, there was no related study try to explore the connection of immune infiltrates and UBE2T, we first study the immune infiltrates and miRNAs in correlation with UBE2T in OC. Correlation between UBE2T in OC expression and abundance of immune infiltrates was statistically significant and the cumulative survive showed that dendritic cell of immune infiltrates statistically significant (P < 0.05) of UBE2T in OC indicating that dendritic cell significantly affecting the prognosis, it is worth further research and exploration. We finally study the miRNAs that correlation with UBE2T in OC. The top 3 among 1169 miRNAs family was hsa-miR-5580-3p, hsa-miR-3652 and hsa-miR-4430 that related to gene UBE2T in OC. Study reported miR-3652 association with oral squamous cell carcinoma prognosis and miR-4430 related to breast cancer cells prognosis30,31. In order to explore the function of the identified 1169 miRNAs, biological enrichment was performed through Funrich database. Biological pathway enriched in glypican pathway, proteoglycan syndecan-mediated signaling events, VEGF and VEGFR signaling network, TRAIL signaling pathway, sphingosine 1-phosphate (S1P) pathway and ErbB signaling pathway. Thus, UBE2T may help us understand the protein disease pathogenesis and progression in future study. Our study found that the expression of UBE2T was significantly increased in OC patients and associated with several clinical features. UBE2T may be a potentially useful prognostic molecular biomarker of bad survival in OC, while further experimental ought to be performed to demonstrate the biologic effect of UBE2T.