免疫原性细胞死亡（Immunogenic Cell Death, ICD）和长链非编码RNA（Long Noncoding RNAs, lncRNAs）均与肿瘤发展密切相关，然而在肝细胞癌（Hepatocellular Carcinoma, HCC）中，ICD相关lncRNAs的作用机制仍不清楚。方法：我们从癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库中收集了365例HCC患者的数据。我们制定了一个ICD相关lncRNAs的预后标志物和一个预测预后的画图表。为了探究潜在机制并提供临床指导，我们基于风险评分得到的亚组进行了生存分析、富集分析、肿瘤微环境分析、肿瘤突变负荷以及药物敏感性预测。

结果：我们构建了一个由7个ICD相关lncRNAs组成的预后标志物。Kaplan-Meier（K-M）生存曲线显示高风险患者的预后结果较差。预测表与不包含风险模型的预测表相比，具有更高的预测价值。富集分析证实了风险lncRNAs与细胞增殖和有丝分裂密切相关。目前用于治疗的大多数免疫检查点（例如PDCD1、CTLA4）在高风险患者中明显升高。肿瘤微环境分析显示高风险组中淋巴细胞（包括自然杀伤细胞、调节性T细胞等）表达差异明显。高风险组中肿瘤突变负荷（Tumor Mutation Burden, TMB）发生率更高（p=0.004）。化疗药物敏感性预测为个体化治疗提供了有效的指导。人类HCC组织的RT-qPCR验证了模型的准确性。

结论：我们利用7个ICD-lncRNAs构建了一个有效的HCC患者预后标志物，为预后评估和个体化治疗提供了指导。版权所有2023年作者。

Both immunogenic cell death (ICD) and long noncoding RNAs (lncRNAs) are strongly associated with tumor development, but the mechanism of action of ICD-associated lncRNAs in hepatocellular carcinoma (HCC) remains unclear.  Methods: We collected data from 365 HCC patients from The Cancer Genome Atlas (TCGA) database. We formulated a prognostic signature of ICD-associated lncRNAs and a nomogram to predict prognosis. To explore the potential mechanisms and provide clinical guidance, survival analysis, enrichment analysis, tumor microenvironment analysis, tumor mutation burden, and drug sensitivity prediction were conducted based on the subgroups obtained from the risk score.

 Results: A prognostic signature of 7 ICD-associated lncRNAs was constructed. Kaplan‒Meier (K‒M) survival curves showed a more unfavorable outcome in high-risk patients. The nomogram had a higher predictive value than the nomogram constructed without the risk model. Enrichment analysis confirmed that risk lncRNAs were closely associated with cell proliferation and mitosis. Most of the immune checkpoints currently used in therapy (e.g., PDCD1, CTLA4) appeared to be elevated in high-risk patients. Tumor microenvironment analysis showed differential expression of lymphocytes (including natural killer cells, regulatory T cells, etc.) in the high-risk group. The tumor mutation burden (TMB) had a higher incidence of mutations in the high-risk group (p=0.004). Chemotherapy drug sensitivity prediction provides effective guidelines for individual therapy. RT‒qPCR of human HCC tissues verified the accuracy of the model.

 Conclusion: We constructed an effective prognostic signature for patients with HCC using seven ICD-lncRNAs, which provides guidance for the prognostic assessment and personalized treatment of patients.

.Copyright 2023 The Author(s).