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整合机器学习以构建与异常可变剪接事件相关的分类器,用于预测肝细胞癌患者的预后和免疫治疗反应。

Integrating machine learning to construct aberrant alternative splicing event related classifiers to predict prognosis and immunotherapy response in patients with hepatocellular carcinoma.

作者信息

Liu Wangrui, Zhao Shuai, Xu Wenhao, Xiang Jianfeng, Li Chuanyu, Li Jun, Ding Han, Zhang Hailiang, Zhang Yichi, Huang Haineng, Wang Jian, Wang Tao, Zhai Bo, Pan Lei

机构信息

Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Pharmacol. 2022 Oct 3;13:1019988. doi: 10.3389/fphar.2022.1019988. eCollection 2022.

Abstract

In hepatocellular carcinoma (HCC), alternative splicing (AS) is related to tumor invasion and progression. We used HCC data from a public database to identify AS subtypes by unsupervised clustering. Through feature analysis of different splicing subtypes and acquisition of the differential alternative splicing events (DASEs) combined with enrichment analysis, the differences in several subtypes were explored, cell function studies have also demonstrated that it plays an important role in HCC. Finally, in keeping with the differences between these subtypes, DASEs identified survival-related AS times, and were used to construct risk proportional regression models. AS was found to be useful for the classification of HCC subtypes, which changed the activity of tumor-related pathways through differential splicing effects, affected the tumor microenvironment, and participated in immune reprogramming. In this study, we described the clinical and molecular characteristics providing a new approach for the personalized treatment of HCC patients.

摘要

在肝细胞癌(HCC)中,可变剪接(AS)与肿瘤侵袭和进展相关。我们使用来自公共数据库的HCC数据,通过无监督聚类来识别AS亚型。通过对不同剪接亚型的特征分析以及获取差异可变剪接事件(DASE)并结合富集分析,探索了几种亚型之间的差异,细胞功能研究也表明其在HCC中起重要作用。最后,根据这些亚型之间的差异,DASE确定了与生存相关的AS时间,并用于构建风险比例回归模型。发现AS对HCC亚型分类有用,它通过差异剪接效应改变肿瘤相关通路的活性,影响肿瘤微环境,并参与免疫重编程。在本研究中,我们描述了临床和分子特征,为HCC患者的个性化治疗提供了一种新方法。

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