由9个m6A调控因子相关lncRNA组成的lncRNA风险模型在肝细胞癌(HCC)中的预后价值

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Zhen Deng, Jiaxing Hou, Hongbo Xu, Zhao Lei, Zhiqiang Li, Hongwei Zhu, Xiao Yu, Zhi Yang, Xiaoxin Jin, Jichun Sun
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引用次数: 1

摘要

肝细胞癌(HCC)是肝脏最常见的原发性恶性肿瘤。尽管有报道称RNA修饰n6 -甲基腺嘌呤(m6A)参与了HCC的癌变,但仍缺乏早期诊断标志物和有希望的个性化治疗靶点。在本研究中,我们发现19个m6A调节因子和34个共表达的lncrna在HCC样本中显著上调;基于这些因素,我们使用LASSO Cox回归分析建立了与9个lncrna和19个m6A调节因子相关的HCC预后信号。Kaplan-Meier生存估计揭示了训练和验证数据集中风险评分与患者OS之间的相关性。ROC曲线表明,基于风险评分的曲线对训练数据集和验证数据集都具有满意的预测效率。多变量Cox比例风险回归分析表明,在训练和验证数据集中,风险评分是一个独立的风险因素。此外,风险评分可以区分HCC患者与正常非癌性样本和不同病理分级的HCC样本。最终,根据GSE101685和GSE112790, 232个mrna与这9个lncrna共表达;这些mrna富集于细胞周期和细胞代谢活动、药物代谢、肝脏疾病相关通路以及一些重要的癌症相关通路,如p53、MAPK、Wnt、RAS等。这9种lncrna在HCC样本中的表达明显高于邻近的非癌样本。总之,通过Consensus Clustering、PCA、ESTIMATE算法、LASSO回归模型、Kaplan-Meier生存评估、ROC曲线分析和多变量Cox比例风险回归模型分析,我们建立了一个由9个m6A调控因子相关lncrna组成的预后标志物,这些标志物可能具有HCC的预后和诊断潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Prognostic Value of a lncRNA Risk Model Consists of 9 m6A Regulator-Related lncRNAs in Hepatocellular Carcinoma (HCC).

The Prognostic Value of a lncRNA Risk Model Consists of 9 m6A Regulator-Related lncRNAs in Hepatocellular Carcinoma (HCC).

The Prognostic Value of a lncRNA Risk Model Consists of 9 m6A Regulator-Related lncRNAs in Hepatocellular Carcinoma (HCC).

The Prognostic Value of a lncRNA Risk Model Consists of 9 m6A Regulator-Related lncRNAs in Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Although the RNA modification N6-methyladenine (m6A) has been reported to be involved in HCC carcinogenesis, early diagnostic markers and promising personalized therapeutic targets are still lacking. In this study, we identified that 19 m6A regulators and 34 co-expressed lncRNAs were significantly upregulated in HCC samples; based on these factors, we established a prognostic signal of HCC associated with 9 lncRNAs and 19 m6A regulators using LASSO Cox regression analysis. Kaplan-Meier survival estimate revealed correlations between the risk scores and patients' OS in the training and validation dataset. The ROC curve demonstrated that the risk score-based curve has satisfactory prediction efficiency for both training and validation datasets. Multivariate Cox's proportional hazard regression analysis indicated that the risk score was an independent risk factor within the training and validation dataset. In addition, the risk score could distinguish HCC patients from normal non-cancerous samples and HCC samples of different pathological grades. Eventually, 232 mRNAs were co-expressed with these 9 lncRNAs according to GSE101685 and GSE112790; these mRNAs were enriched in cell cycle and cell metabolic activities, drug metabolism, liver disease-related pathways, and some important cancer related pathways such as p53, MAPK, Wnt, RAS and so forth. The expression of the 9 lncRNAs was significantly higher in HCC samples than that in the neighboring non-cancerous samples. Altogether, by using the Consensus Clustering, PCA, ESTIMATE algorithm, LASSO regression model, Kaplan-Meier survival assessment, ROC curve analysis, and multivariate Cox's proportional hazard regression model analysis, we established a prognostic marker consisting of 9 m6A regulator-related lncRNAs that markers may have prognostic and diagnostic potential for HCC.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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