Pyroptosis-Related LncRNA Signature Predicts Prognosis and Is Associated With Immune Infiltration in Hepatocellular Carcinoma.

Pyroptosis-Related LncRNA Signature Predicts Prognosis and Is Associated With Immune Infiltration in Hepatocellular Carcinoma.
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细胞焦亡相关的 LncRNA 特征可预测预后并与肝细胞癌的免疫浸润相关

DOI:
10.3389/fonc.2022.794034
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发表时间:
2022
影响因子:
4.7
通讯作者:
Wei D
Wei D
中科院分区:
医学3区
文献类型:
--
作者:
Liu ZK;Wu KF;Zhang RY;Kong LM;Shang RZ;Lv JJ;Li C;Lu M;Yong YL;Zhang C;Zheng NS;Li YH;Chen ZN;Bian H;Wei D

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焦亡是一种炎症形式的程序性细胞死亡,涉及各种癌症,包括肝细胞癌(HCC)。长链非编码RNA(lncRNA)最近被证实是调节细胞凋亡的关键介质。然而,肝细胞癌中与肝细胞凋亡相关的lncRNA的作用及其与预后的关系尚未见报道。在这项研究中,我们构建了一个预后的基础上,肝细胞癌中的热解相关的差异表达lncRNA的签名。基于来自癌症基因组图谱的HCC数据构建了热解相关mRNA-lncRNA的共表达网络。进行考克斯回归分析以在训练组群中构建热解相关的lncRNA标签(PRlncSig),其随后在测试组群和两个组群的组合中得到验证。Kaplan-Meier分析显示,高危组患者的生存时间较短。受试者工作特征曲线和主成分分析进一步验证了PRlncSig模型的准确性。此外,外部队列验证证实了PRlncSig的稳健性。此外,建立了基于PRlncSig评分和临床特征的列线图,并显示其具有稳健的预测能力。此外,基因集富集分析显示,与低风险组相比,高风险组的RNA降解、细胞周期、WNT信号通路和许多免疫过程显著富集。此外,免疫细胞亚群,免疫检查点基因的表达以及对化疗和免疫治疗的反应在高风险组和低风险组之间存在显着差异。最后,通过实时定量PCR验证了特征中五种lncRNA的表达水平。综上所述,我们的PRlncSig模型对HCC患者的预后显示出显著的预测价值,并且可以为个体化免疫治疗提供临床指导。
Pyroptosis is an inflammatory form of programmed cell death that is involved in various cancers, including hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) were recently verified as crucial mediators in the regulation of pyroptosis. However, the role of pyroptosis-related lncRNAs in HCC and their associations with prognosis have not been reported. In this study, we constructed a prognostic signature based on pyroptosis-related differentially expressed lncRNAs in HCC. A co-expression network of pyroptosis-related mRNAs–lncRNAs was constructed based on HCC data from The Cancer Genome Atlas. Cox regression analyses were performed to construct a pyroptosis-related lncRNA signature (PRlncSig) in a training cohort, which was subsequently validated in a testing cohort and a combination of the two cohorts. Kaplan–Meier analyses revealed that patients in the high-risk group had poorer survival times. Receiver operating characteristic curve and principal component analyses further verified the accuracy of the PRlncSig model. Besides, the external cohort validation confirmed the robustness of PRlncSig. Furthermore, a nomogram based on the PRlncSig score and clinical characteristics was established and shown to have robust prediction ability. In addition, gene set enrichment analysis revealed that the RNA degradation, the cell cycle, the WNT signaling pathway, and numerous immune processes were significantly enriched in the high-risk group compared to the low-risk group. Moreover, the immune cell subpopulations, the expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. Finally, the expression levels of the five lncRNAs in the signature were validated by quantitative real-time PCR. In summary, our PRlncSig model shows significant predictive value with respect to prognosis of HCC patients and could provide clinical guidance for individualized immunotherapy.
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