Cuproptosis-related lncRNAs predict the clinical outcome and immune characteristics of hepatocellular carcinoma.
Cuproptosis-related lncRNAs predict the clinical outcome and immune characteristics of hepatocellular carcinoma.
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DOI：
10.3389/fgene.2022.972212
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发表时间：
2022
影响因子：
3.7
通讯作者：
Cheng, Shuqun
中科院分区：
文献类型：
--
作者：
Zhu, Hongfei;Mao, Feifei;Wang, Kang;Feng, Jinkai;Cheng, Shuqun
铜中毒是一种新型的铜依赖性非凋亡性细胞死亡形式，由脂酰化线粒体蛋白的聚集和Fe-S簇蛋白的不稳定性诱导。然而，铜中毒相关的长非编码RNA（CRLncRNA）在肝细胞癌（HCC）中的作用尚未明确阐明。在这项研究中，我们确定并表征了肝细胞癌中铜中毒相关的lncRNA。筛选后，从癌症基因组图谱（TCGA）中获得343例具有基因转录组数据和临床数据的HCC病例用于分析。进行单变量和多变量考克斯比例风险分析以建立预后性铜中毒相关lncRNA特征（CRlncSig）。我们建立了一个由9个铜中毒相关lncRNA组成的铜中毒相关模型：GSEC，AL158166.1，AC005479.2，AL365361.1，AC026412.3，AL031985.3，LINC 00426，AC009974.2，AC245060.7，并在内部队列中进行了验证。按CRlncSig分层的高危组与不良预后显著相关（p < 0.001）。1年、3年和5年生存期的受试者工作特征曲线下面积（AUC）分别为0.813、0.789和0.752。此外，包括CRlncSig与临床病理因素的预后诺模图具有良好的预测能力。此外，GO和KEGG富集分析提示CRlncSig参与多种肿瘤发生和免疫相关通路。此外，我们发现，基于风险模型，高风险组和低风险组之间的肿瘤微环境、免疫浸润、免疫功能和药物反应存在显著差异。这些结果突出了铜中毒相关lncRNA对HCC患者预后的价值，并提供了对铜中毒相关lncRNA的分子和免疫特征的深入了解，这可能在患者管理和免疫治疗中发挥重要作用。
Cuproptosis, as a novel copper-dependent and non-apoptotic form of cell death, is induced by aggregation of lipoylated mitochondrial proteins and the instability of Fe-S cluster proteins. However, the role of cuproptosis-related long noncoding RNAs (CRLncRNAs) in hepatocellular carcinoma (HCC) has not been clearly elucidated. In this study, we identified and characterized cuproptosis-related lncRNAs in HCC. 343 HCC cases from The Cancer Genome Atlas (TCGA) with gene transcriptome data and clinical data were obtained for analysis after the screening. Univariate and multivariate Cox proportional hazards analyses were performed to establish a prognostic cuproptosis-related lncRNA signature (CRlncSig). We established a prognosis-related model consisting of nine cuproptosis-related lncRNAs: GSEC, AL158166.1, AC005479.2, AL365361.1, AC026412.3, AL031985.3, LINC00426, AC009974.2, AC245060.7, which was validated in the internal cohort. High-risk group stratified by the CRlncSig was significantly related to poor prognosis (p < 0.001). The area under the receiver operating characteristic curve (AUC) of 1 year, 3 years, and 5 years of survival were 0.813, 0.789, and 0.752, respectively. Furthermore, a prognostic nomogram including CRlncSig with clinicopathologic factors was built with favorable predictive power. In addition, GO and KEGG enrichment analysis suggested that CRlncSig was involved in many carcinogenesis and immune-related pathways. Additionally, we found that tumor microenvironment, immune infiltration, immune function, and drug response were significantly different between the high-risk and low-risk groups based on the risk model. These results highlight the value of cuproptosis-related lncRNAs on prognosis for HCC patients and provide insight into molecular and immune features underlying cuproptosis-related lncRNAs, which might play an important role in patient management and immunotherapy.
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影响因子：
5
作者：
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通讯作者：
Oliveri V
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5
作者：
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Flicek P
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64.5
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Liu J;Lichtenberg T;Hoadley KA;Poisson LM;Lazar AJ;Cherniack AD;Kovatich AJ;Benz CC;Levine DA;Lee AV;Omberg L;Wolf DM;Shriver CD;Thorsson V;Cancer Genome Atlas Research Network;Hu H
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影响因子：
9
作者：
Lau, WY;Leung, TWT;Tang, AMY
通讯作者：
Tang, AMY