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基于生物信息学方法预测肝细胞癌的预后和铁死亡分子机制。

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods.

机构信息

Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.

出版信息

Comput Math Methods Med. 2022 Jun 21;2022:4558782. doi: 10.1155/2022/4558782. eCollection 2022.

DOI:10.1155/2022/4558782
PMID:35774297
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9239824/
Abstract

BACKGROUND

As an iron-dependent type of programmed cell death, ferroptosis plays an important role in the pathogenesis and progression of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) have been linked to the prognosis of patients with HCC in a number of studies. Nevertheless, the predictive value of lncRNAs (FRLs) associated with ferroptosis in HCC has not been fully elucidated.

METHODS

Download RNA sequencing data and clinical profiles of HCC patients from The Cancer Genome Atlas (TCGA) database. The FRLs associated with prognosis were determined by Pearson's correlation analysis. After that, prognostic signature for FRLs was established using Cox and LASSO regression analyses. Meanwhile, survival analysis, correlation analysis of clinicopathological features, Cox regression, receiver operating characteristic (ROC) curve, and nomogram were used to analyze the FRL signature's predictive capacity. The relationship between signature risk score, immune cell infiltration, and chemotherapy drug sensitivity is further studied.

RESULTS

In total, 93 FRLs were found to be of prognostic value in patients with HCC. A five-FRL signature comprising AC015908.3, LINC01138, AC009283.1, Z83851.1, and LUCAT1 was created in order to enhance the prognosis prediction with HCC patients. The signature demonstrated a good predictive potency, according to the Kaplan-Meier and ROC curves. The five-FRL signature was found to be a risk factor independent of various clinical factors using Cox regression and stratified survival analysis. The high-risk group was shown to be enriched in tumorigenesis and immune-related pathways according to GSEA analysis. Additionally, immune cell infiltration, immune checkpoint molecules, and half-inhibitory concentrations differed considerably between risk groups, implying that this signature could be used to evaluate the clinical efficacy of chemotherapy and immunotherapy.

CONCLUSION

The five-FRL risk signature is helpful for assessing the prognosis of HCC patients and improving therapy options, so it can be further applied clinically.

摘要

背景

铁依赖性细胞程序性死亡方式之一的铁死亡在肝细胞癌(HCC)的发病机制和进展中起着重要作用。长链非编码 RNA(lncRNA)在多项研究中与 HCC 患者的预后相关。然而,lncRNA(FRL)与 HCC 中铁死亡的预测价值尚未得到充分阐明。

方法

从癌症基因组图谱(TCGA)数据库下载 HCC 患者的 RNA 测序数据和临床资料。通过 Pearson 相关性分析确定与预后相关的 FRL。然后,利用 Cox 和 LASSO 回归分析建立 FRL 预后标志。同时,采用生存分析、临床病理特征相关性分析、Cox 回归、接受者操作特征(ROC)曲线和列线图分析 FRL 标志的预测能力。进一步研究了标志风险评分与免疫细胞浸润和化疗药物敏感性的关系。

结果

共发现 93 个与 HCC 患者预后相关的 FRL。为了提高 HCC 患者的预后预测能力,构建了一个包含 AC015908.3、LINC01138、AC009283.1、Z83851.1 和 LUCAT1 的 5-FRL 标志。Kaplan-Meier 和 ROC 曲线表明该标志具有良好的预测能力。Cox 回归和分层生存分析表明,5-FRL 标志是独立于各种临床因素的危险因素。GSEA 分析表明,高风险组在肿瘤发生和免疫相关途径中富集。此外,风险组之间的免疫细胞浸润、免疫检查点分子和半抑制浓度差异显著,表明该标志可用于评估化疗和免疫治疗的临床疗效。

结论

该 5-FRL 风险标志有助于评估 HCC 患者的预后,并改善治疗方案,因此可以进一步在临床上应用。

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