Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma.
Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma.
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DOI：
10.3389/fimmu.2021.719175
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yan Y
中科院分区：
文献类型：
--
作者：
Xu Z;Peng B;Liang Q;Chen X;Cai Y;Zeng S;Gao K;Wang X;Yi Q;Gong Z;Yan Y
铁凋亡是一种铁依赖性细胞死亡过程，在包括肝细胞癌（HCC）在内的癌症的发生和发展中起着重要的调节作用。此外，围绕异常表达的长链非编码rna （lncRNAs）驱动HCC发生和进展的分子事件引起了越来越多的关注。然而，HCC患者中与铁细胞凋亡相关的lncRNA预后特征的研究仍然缺乏。在本研究中，我们利用Pearson检验法对来自the Cancer Genome Atlas （TCGA）的374例HCC和50例正常肝脏样本中差异表达的lncrna与凋亡相关基因的相关性进行了评估，从而鉴定出24例凋亡相关的差异表达lncrna。使用最小绝对收缩和选择算子（LASSO）算法和Cox回归模型构建并验证TCGA训练数据集和GEO测试数据集（GSE40144）的预后风险评分模型。一个基于9个lncrna的特征（CTD-2033A16.3、CTD-2116N20.1、CTD-2510F5.4、DDX11-AS1、LINC00942、LINC01224、LINC01231、LINC01508和ZFPM2-AS1）被确定为独立于多个临床病理参数的肝癌铁中毒相关预后模型。此外，根据9 - lncrna预后特征将HCC患者分为高危组和低危组。基因集富集分析富集分析显示，基于lncrna的信号可能通过干扰肿瘤坏死因子α/核因子κ b、白细胞介素2/信号转导和转录激活因子5、细胞因子/细胞因子受体信号通路调控肝癌免疫微环境。浸润性免疫细胞亚型，如静息记忆CD4(+) T细胞、滤泡辅助性T细胞、调节性T细胞、M0巨噬细胞，在高危组和低危组之间的Spearman相关分析均有显著差异。此外，在高危组B7H3免疫检查点分子的表达显著增加。我们的研究结果为HCC中铁细胞凋亡相关的lncrna提供了有希望的见解，并为患者的预后和免疫反应提供了个性化的预测工具。
Ferroptosis is an iron-dependent cell death process that plays important regulatory roles in the occurrence and development of cancers, including hepatocellular carcinoma (HCC). Moreover, the molecular events surrounding aberrantly expressed long non-coding RNAs (lncRNAs) that drive HCC initiation and progression have attracted increasing attention. However, research on ferroptosis-related lncRNA prognostic signature in patients with HCC is still lacking. In this study, the association between differentially expressed lncRNAs and ferroptosis-related genes, in 374 HCC and 50 normal hepatic samples obtained from The Cancer Genome Atlas (TCGA), was evaluated using Pearson’s test, thereby identifying 24 ferroptosis-related differentially expressed lncRNAs. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression model were used to construct and validate a prognostic risk score model from both TCGA training dataset and GEO testing dataset (GSE40144). A nine-lncRNA-based signature (CTD-2033A16.3, CTD-2116N20.1, CTD-2510F5.4, DDX11-AS1, LINC00942, LINC01224, LINC01231, LINC01508, and ZFPM2-AS1) was identified as the ferroptosis-related prognostic model for HCC, independent of multiple clinicopathological parameters. In addition, the HCC patients were divided into high-risk and low-risk groups according to the nine-lncRNA prognostic signature. The gene set enrichment analysis enrichment analysis revealed that the lncRNA-based signature might regulate the HCC immune microenvironment by interfering with tumor necrosis factor α/nuclear factor kappa-B, interleukin 2/signal transducers and activators of transcription 5, and cytokine/cytokine receptor signaling pathways. The infiltrating immune cell subtypes, such as resting memory CD4(+) T cells, follicular helper T cells, regulatory T cells, and M0 macrophages, were all significantly different between the high-risk group and the low-risk group as indicated in Spearman’s correlation analysis. Moreover, a substantial increase in the expression of B7H3 immune checkpoint molecule was found in the high-risk group. Our findings provided a promising insight into ferroptosis-related lncRNAs in HCC and a personalized prediction tool for prognosis and immune responses in patients.
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影响因子：
--
作者：
He Y;Wang X
通讯作者：
Wang X
影响因子：
7.3
作者：
Lurje I;Werner W;Mohr R;Roderburg C;Tacke F;Hammerich L
通讯作者：
Hammerich L
铁死亡通过circ0097009/miR-1261/SLC7A11轴参与肝细胞癌的进展
影响因子：
--
作者：
Lyu N;Zeng Y;Kong Y;Chen Q;Deng H;Ou S;Bai Y;Tang H;Wang X;Zhao M
通讯作者：
Zhao M
影响因子：
4.7
作者：
Li, Wang;Chen, Qi-Feng;Huang, Zi-Lin
通讯作者：
Huang, Zi-Lin
影响因子：
5.6
作者：
Pandelides, Zacharias;Thornton, Cammi;Ashpole, Nicole M.
通讯作者：
Ashpole, Nicole M.