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染色质调节因子的特征鉴定揭示了肝细胞癌的预后和异质性。

Characterization of chromatin regulators identified prognosis and heterogeneity in hepatocellular carcinoma.

作者信息

Dai Yin-Wei, Chen Han-Bin, Pan Ya-Ting, Lv Lin-Xi, Wang Wei-Ming, Chen Xiao-Hu, Zhou Xiang

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Department of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Front Oncol. 2022 Sep 9;12:1002781. doi: 10.3389/fonc.2022.1002781. eCollection 2022.

Abstract

Liver carcinogenesis is a multiprocess that involves complicated interactions between genetics, epigenetics, and transcriptomic alterations. Aberrant chromatin regulator (CR) expressions, which are vital regulatory epigenetics, have been found to be associated with multiple biological processes. Nevertheless, the impression of CRs on tumor microenvironment remodeling and hepatocellular carcinoma (HCC) prognosis remains obscure. Thus, this study aimed to systematically analyze CR-related patterns and their correlation with genomic features, metabolism, cuproptosis activity, and clinicopathological features of patients with HCC in The Cancer Genome Atlas, International Cancer Genome Consortium-LIRI-JP cohort, and GSE14520 that utilized unsupervised consensus clustering. Three CR-related patterns were recognized, and the CRs phenotype-related gene signature (CRsscore) was developed using the least absolute shrinkage and selection operator-Cox regression and multivariate Cox algorithms to represent the individual CR-related pattern. Additionally, the CRsscore was an independent prognostic index that served as a fine predictor for energy metabolism and cuproptosis activity in HCC. Accordingly, describing a wide landscape of CR characteristics may assist us to illustrate the sealed association between epigenetics, energy metabolism, and cuproptosis activity. This study may discern new tumor therapeutic targets and exploit personalized therapy for patients.

摘要

肝癌发生是一个多过程,涉及遗传学、表观遗传学和转录组改变之间复杂的相互作用。异常染色质调节因子(CR)的表达是重要的表观遗传调控因素,已发现其与多种生物学过程相关。然而,CR对肿瘤微环境重塑和肝细胞癌(HCC)预后的影响仍不清楚。因此,本研究旨在利用无监督一致性聚类,系统分析癌症基因组图谱、国际癌症基因组联盟-LIRI-JP队列和GSE14520中HCC患者的CR相关模式及其与基因组特征、代谢、铜死亡活性和临床病理特征的相关性。识别出三种CR相关模式,并使用最小绝对收缩和选择算子- Cox回归及多变量Cox算法开发了CRs表型相关基因特征(CRsscore),以代表个体CR相关模式。此外,CRsscore是一个独立的预后指标,可作为HCC能量代谢和铜死亡活性的良好预测指标。因此,描述CR特征的广泛图景可能有助于我们阐明表观遗传学、能量代谢和铜死亡活性之间的紧密联系。本研究可能识别出新的肿瘤治疗靶点,并为患者开发个性化治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e74/9505021/b8aaa447e0fd/fonc-12-1002781-g001.jpg

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