Identification and validation of UBE2B as a prognostic biomarker promoting the development of esophageal carcinomas

Han Ding; Jia-Cheng Xu; Zhi-Guo Ding; Lin-Feng Wu; Yan-Bo Liu; Yi-Fei Zhang; Tian-Yin Chen; Yi-Qun Zhang; Ping-Hong Zhou

doi:10.3389/fimmu.2024.1295305

Identification and validation of UBE2B as a prognostic biomarker promoting the development of esophageal carcinomas

Front Immunol. 2024 Feb 28:15:1295305. doi: 10.3389/fimmu.2024.1295305. eCollection 2024.

Authors

Han Ding^#^{1

2}, Jia-Cheng Xu^#³, Zhi-Guo Ding^#⁴, Lin-Feng Wu^#^{1

2}, Yan-Bo Liu^{1

2}, Yi-Fei Zhang^{1

2}, Tian-Yin Chen^#^{1

2}, Yi-Qun Zhang^#^{1

2}, Ping-Hong Zhou^#^{1

2}

Affiliations

¹ Department of Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Endoscopy, Shanghai Collaborative Innovation Center, Shanghai, China.
³ Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
⁴ Department of General Surgery, The Third People's Hospital of Yangzhou, Yangzhou, Jiangsu, China.

^# Contributed equally.

Abstract

Introduction: Ubiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA).

Methods: To identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development.

Results: Through univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down.

Conclusions: To summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA.

Keywords: UBE2B; bioinformatics; esophageal carcinoma; immune infiltration; prognostic biomarker.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes
Biomarkers
Carcinoma*
Esophageal Neoplasms* / genetics
Humans
Oncogenes
Prognosis
Ubiquitin-Conjugating Enzymes / genetics

Substances

Biomarkers
UBE2B protein, human
Ubiquitin-Conjugating Enzymes

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the National Natural Science Foundation of China (No. 82172787).