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基于生物信息学分析的E3泛素连接酶相关预后基因的鉴定及子宫颈癌预测模型的构建

Identification of E3 ubiquitin ligase-associated prognostic genes and construction of a prediction model for uterine cervical cancer based on bioinformatics analysis.

作者信息

Yan Zhengchao, Yu Jingwei, Wang Shuyuan, Wen Weibo, Xin Mengyuan, Li Xiangdan

机构信息

Department of Morphological Experiment Center, Medical College of Yanbian University, No. 977, Gongyuan Road, Yanji, 133000, Jilin, China.

出版信息

Discov Oncol. 2024 Aug 31;15(1):395. doi: 10.1007/s12672-024-01271-y.

Abstract

E3 ligases are engaged in a variety of physiological processes within cells and use ubiquitin-labeled substrates to control their activity and stability. Although some research has indicated that E3 ligases or particular substrates have an impact on the treatment that cervical cancer patients get after their diagnosis, The exact purpose of these enzymes in the occurrence and evolution of cancer of the cervical region (CC) is not clear. In order to extract and analyze relevant mRNA gene expression data as well as clinical patient data, we used open databases. A reliable risk prediction model was developed by applying the least absolute shrinkage and selection operator (LASSO) technique in conjunction with Cox regression analysis. Column-line plots were combined to analyze the predictive model, and the GSE44001 dataset served as an external validation.Four gene models:proteasome (prosome, macropain) 26S subunit, non-ATPase, 14(PSMD14),proteasome (prosome, macropain) subunit, alpha type, 4(PSMA4,),zinc finger and BTB domain containing 16(ZBTB16),and ankyrin repeat domain 9(ANKRD9). Gene expression levels in both healthy and cancerous tissues have been confirmed by the HPA database. Next, the investigation focused on immunological state and tumor mutation load. The high-risk group and Cluster B had distinct levels of immune cell infiltration and a worse prognosis. Additionally, KEGG and GO analyses of differentially expressed genes (DEGs) between the high- and low-risk groups were performed, as well as tumor microenvironment (TME) investigations. Targeting E3 ligases may be an efficient strategy to treat cervical cancer (CC), according to a novel and comprehensive E3 ubiquitination ligase-associated gene model that has been presented.

摘要

E3 泛素连接酶参与细胞内多种生理过程,并利用泛素标记的底物来控制其活性和稳定性。尽管一些研究表明 E3 泛素连接酶或特定底物对宫颈癌患者确诊后的治疗有影响,但这些酶在宫颈癌(CC)发生和发展中的确切作用尚不清楚。为了提取和分析相关的 mRNA 基因表达数据以及临床患者数据,我们使用了开放数据库。通过应用最小绝对收缩和选择算子(LASSO)技术结合 Cox 回归分析,构建了一个可靠的风险预测模型。结合列线图分析预测模型,并使用 GSE44001 数据集进行外部验证。四个基因模型:蛋白酶体(prosome,巨蛋白酶)26S 亚基,非 ATP 酶,14(PSMD14)、蛋白酶体(prosome,巨蛋白酶)亚基,α 型,4(PSMA4)、含锌指和 BTB 结构域 16(ZBTB16)以及锚蛋白重复结构域 9(ANKRD9)。健康组织和癌组织中的基因表达水平已通过 HPA 数据库得到证实。接下来,研究集中在免疫状态和肿瘤突变负荷上。高危组和 B 簇的免疫细胞浸润水平不同,预后较差。此外,还对高危组和低危组之间的差异表达基因(DEG)进行了KEGG和GO分析,以及肿瘤微环境(TME)研究。根据提出的一种新颖且全面的 E3 泛素化连接酶相关基因模型,靶向 E3 泛素连接酶可能是治疗宫颈癌(CC)的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d0/11365898/2eab8cfafe06/12672_2024_1271_Fig1_HTML.jpg

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