Identification of a pyroptosis-related long noncoding RNA signature for determining the prognosis and immune status of hepatocellular carcinoma patients.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Shaohua Xu, Guoxu Fang
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引用次数: 0

Abstract

Background: Despite improvements in cancer screening and diagnosis, hepatocellular carcinoma (HCC) is still diagnosed at an advanced stage, and the prognosis is worse than that of early HCC patients. Therefore, better molecular markers and therapeutic targets in HCC are required.

Objectives: We investigated the predictive value of pyroptosis-related long noncoding RNAs (lncRNAs) in HCC and the effects of these lncRNAs on the immune microenvironment of HCC.

Material and methods: RNA sequencing data of HCC patients were extracted from The Cancer Genome Atlas (TCGA) database to identify differentially expressed pyroptosis-related lncRNAs related to overall survival (OS). A model was established to verify the character of pyroptosis-associated lncRNAs in the tumor microenvironment, and their prognostic value was evaluated.

Results: A total of 721 PR lncRNAs were identified based on the analysis of the TCGA database. Univariate Cox analysis revealed 37 survival-related PRlncRNAs with prognostic values. As a result of least absolute shrinkage and selection operator (LASSO) regression analysis, 'ELFN-AS1', AC099850.3, AC073389.3, 'HPN-AS1', AC009283.1, and AL139289.1 showed prognostic value. Kaplan-Meier analysis indicated that the OS of the high-risk set was worse than those of the low-risk set in both the training and testing cohorts. Univariate and multivariate analyses revealed that the risk score was a better independent prognostic factor than the stage. The precision of the lncRNA signature was confirmed using receiver operating characteristic curve (ROC) analysis. Immuneand metabolism-related pathways were enriched in both the lowand high-risk groups. Gene set enrichment analysis suggested that the identified lncRNAs regulate HCC tumorigenesis and prognosis by modulating metabolism. Various algorithms were used to confirm the significant differences in immune cells between these 2 groups.

Conclusions: These findings could contribute to the development and validation of favorable biomarkers, improve the prognosis and survival of HCC, and help in developed individualized treatment plans for HCC.

鉴定用于确定肝细胞癌患者预后和免疫状态的热病相关长非编码 RNA 标志。
背景:尽管癌症筛查和诊断有所改善,但肝细胞癌(HCC)的诊断仍处于晚期,而且预后比早期 HCC 患者更差。因此,需要更好的 HCC 分子标记物和治疗靶点:材料与方法:HCC患者的RNA测序数据显示,HCC患者中的非编码RNAs(lncRNAs)与HCC的免疫微环境有关:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中提取HCC患者的RNA测序数据,以鉴定与总生存期(OS)相关的不同表达的热释相关lncRNA。建立了一个模型来验证肿瘤微环境中热休克相关lncRNAs的特征,并评估了它们的预后价值:结果:根据对TCGA数据库的分析,共鉴定出721个PR lncRNA。单变量Cox分析显示,37个与生存相关的PRlncRNA具有预后价值。最小绝对收缩和选择算子(LASSO)回归分析结果显示,'ELFN-AS1'、AC099850.3、AC073389.3、'HPN-AS1'、AC009283.1和AL139289.1具有预后价值。Kaplan-Meier分析表明,在训练组和测试组中,高风险组的OS均低于低风险组。单变量和多变量分析显示,风险评分是比分期更好的独立预后因素。接受者操作特征曲线(ROC)分析证实了lncRNA特征的精确性。免疫和代谢相关通路在低危和高危组中都有富集。基因集富集分析表明,所发现的lncRNA通过调节代谢来调控HCC肿瘤的发生和预后。通过各种算法确认了这两组之间免疫细胞的显著差异:这些发现有助于开发和验证有利的生物标志物,改善 HCC 的预后和存活率,并帮助制定 HCC 的个体化治疗方案。
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来源期刊
Advances in Clinical and Experimental Medicine
Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.70
自引率
4.80%
发文量
153
审稿时长
6-12 weeks
期刊介绍: Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.
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