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鉴定和验证 UBE2B 作为一种促进食管癌发展的预后生物标志物。

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

机构信息

Department of Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Endoscopy, Shanghai Collaborative Innovation Center, Shanghai, China.

出版信息

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

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.

摘要

简介

泛素化是人类中一种至关重要的生物学机制,对调节重要的生物过程至关重要,已被认为是癌症治疗的一个有前途的焦点。我们在这项研究中的目标是发现可能与泛素化相关的潜在酶,这些酶可能成为食管癌(ESCA)患者的治疗靶点。

方法

为了鉴定与 ESCA 预后相关的基因,我们检查了 TCGA 数据库中 ESCA 患者的 mRNA 测序数据。通过生物信息学分析进一步研究候选基因在 ESCA 中的作用。随后,我们进行了生物学测定来评估其对 ESCA 发展的影响。

结果

通过单变量 Cox 回归分析,我们确定泛素连接酶 E2 B(UBE2B)是一种与 ESCA 预后相关的潜在基因。UBE2B 表现出显著的上调,并且在 ESCA 以及其他癌症类型中与生存结局相关。此外,UBE2B 被观察到参与 ESCA 发展相关的各种生物学途径,包括 TNF-a 信号通过 NF-κB、上皮-间充质转化、炎症反应和缺氧。此外,还涉及免疫相关途径,如 B 细胞激活(GO:0042113)、B 细胞受体信号通路(GO:0050853)和 B 细胞介导的免疫(GO:0019724)。发现 UBE2B 的高表达与几种 T 细胞(CD8 T 细胞、Th1 细胞)和巨噬细胞的增加有关,而效应记忆 T 细胞(Tem)和 Th17 细胞减少。此外,UBE2B 显示出作为 ESCA 的预后生物标志物的潜力,表现出高灵敏度和特异性。值得注意的是,当敲低 UBE2B 的表达时,ESCA 细胞的增殖和迁移得到有效抑制。

结论

总之,这项研究对深入了解 UBE2B 在 ESCA 中的作用有了新的认识。UBE2B 可能是一种具有良好预测和诊断 ESCA 能力的癌基因。因此,这一发现突出了靶向 UBE2B 作为治疗 ESCA 患者的可行方法的可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc85/10932980/9402061b3d69/fimmu-15-1295305-g001.jpg

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