Ubiquitination, SUMOylation, and NEDDylation related genes serve as prognostic and therapeutic biomarkers for oral squamous cell carcinoma

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-01-17 DOI:10.1111/jop.13508

Shi-Zhou Deng, Xuechen Wu, Lingshu Kong, Bo Cheng, Lin Dai

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Abstract

Background

Ubiquitination, small ubiquitin-related modifiers, and NEDDylation are now found to function in cancer biology; however, its role in the oral cancer patients remains unclear.

Methods

A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of ubiquitin and ubiquitin-like (UB/UBL) genes. A UB/UBL-related risk score was developed via correlation analyses, univariate Cox regression, and multivariate Cox regression. Nomogram analysis evaluates the model's prediction performance. The drug sensitivity analysis, immune profiles of UB/UBL-classified oral squamous cell carcinoma (OSCC) patients, and their related function pathway were investigated, and the role of UB/UBL-related genes in drug therapy was analyzed.

Results

A total of six prognostic UB/UBL-related genes were obtained. PSMD3, PCGF2, and H2BC10 were significantly downregulated in OSCC tissue and associated with longer survival time. OSCC patients in the high-risk group showed a significantly lower overall survival and enriched in cancer-related pathways. The prognostic potential of genes associated with UB/UBL was discovered, and patients with high-risk scores showed an increase of protumor immune infiltrates and a high expression of immune checkpoints. Moreover, the area under the curve of the annual survival rate was 0.616, 0.671, and 0.673, respectively. Besides, patients in the high-risk group are more sensitive to docetaxel, doxorubicin, and methotrexate therapy.

Conclusions

We construct a prognosis model for OSCC patients with UB/UBL-related genes and try to find a new approach to treating oral cancer patients. The UB/UBL-related signature is helpful in developing new tumor markers, prognostic prediction, and in guiding treatment for OSCC patients.

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泛素化、SUMOylation 和 NEDDylation 相关基因可作为口腔鳞状细胞癌的预后和治疗生物标志物。

背景：泛素化、小泛素相关修饰物和 NEDDylation 目前在癌症生物学中发挥着作用，但其在口腔癌患者中的作用仍不清楚：目前已发现泛素化、泛素相关小修饰因子和NEDDylation在癌症生物学中发挥作用，但其在口腔癌患者中的作用仍不清楚：方法：整合了一套生物信息学工具，分析泛素和泛素样（UB/UBL）基因的表达和预后意义。通过相关性分析、单变量 Cox 回归和多变量 Cox 回归，得出了 UB/UBL 相关风险评分。提名图分析评估了模型的预测性能。研究了药物敏感性分析、UB/UBL分类口腔鳞状细胞癌（OSCC）患者的免疫特征及其相关功能通路，并分析了UB/UBL相关基因在药物治疗中的作用：结果：共获得6个预后UB/UBL相关基因。PSMD3、PCGF2和H2BC10在OSCC组织中明显下调，并与较长的生存时间相关。高危组中的OSCC患者总生存率明显较低，且富集于癌症相关通路。发现了与UB/UBL相关基因的预后潜力，高风险评分的患者表现出原发肿瘤免疫浸润的增加和免疫检查点的高表达。此外，年生存率曲线下面积分别为 0.616、0.671 和 0.673。此外，高风险组患者对多西他赛、多柔比星和甲氨蝶呤治疗更敏感：结论：我们利用 UB/UBL 相关基因构建了 OSCC 患者的预后模型，并试图找到治疗口腔癌患者的新方法。UB/UBL相关特征有助于开发新的肿瘤标记物、预测预后以及指导OSCC患者的治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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