Background: Hepatocellular carcinoma (HCC) is among malignancies with the highest fatality toll globally and minimal therapeutic options. Necroptosis is a programmed form of necrosis or inflammatory cell death, which can affect prognosis and microenvironmental status of HCC. Therefore, we aimed to explore the prognostic value of necroptosis-related lncRNAs (NRLs) in HCC and the role of the tumor microenvironment (TME) in immunotherapy. Methods: The RNA-sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). NRLs were identified by Pearson correlation analysis. The signature was constructed using the LASSO-Cox regression analysis and evaluated using the receiver operating characteristic curve (ROC) and the area under the Kaplan-Meier curve. The nomogram was built based on clinical information and risk score. Gene set enrichment analysis (GSEA), immunoassay, half-maximum inhibitory concentration (IC50) analysis of the risk group, and the HCC subtype identification based on NRLs were also carried out. Finally, we detected the expression of lncRNAs in HCC tissues and cell lines in vitro. Results: A total of 508 NRLs were screened out, and seven NRLs were constructed as a risk stratification system to classify patients into distinct low- and high-risk groups. Patients in the high-risk group had a significantly lower overall survival (OS) than those in the low-risk group. Using multivariate Cox regression analysis, we found that the risk score was an independent predictor of OS. Functional analysis showed that the immune status of different patients was different. The IC50 analysis of chemotherapy demonstrated that patients in the high-risk group were more sensitive to commonly prescribed drugs. qRT-PCR showed that three high-risk lncRNAs were upregulated in drug-resistant cells, and the expression in HCC tissues was higher than that in adjacent tissues. Conclusion: The prediction signature developed in this study can be used to assess the prognosis and microenvironment of HCC patients, and serve as a new benchmark for HCC treatment selection.

中文翻译：

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肝细胞癌中坏死性凋亡相关 LncRNA 特征的鉴定和验证用于预后估计和微环境状态。

背景：肝细胞癌 (HCC) 是全球死亡率最高且治疗选择最少的恶性肿瘤之一。坏死性凋亡是一种程序性的坏死或炎性细胞死亡，可影响 HCC 的预后和微环境状态。因此，我们旨在探讨坏死性凋亡相关 lncRNA (NRL) 在 HCC 中的预后价值以及肿瘤微环境 (TME) 在免疫治疗中的作用。方法：RNA测序数据和临床信息从癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）下载。NRL 通过 Pearson 相关分析确定。使用 LASSO-Cox 回归分析构建签名，并使用接收器操作特征曲线 (ROC) 和 Kaplan-Meier 曲线下面积进行评估。列线图是根据临床信息和风险评分构建的。还进行了风险组的基因集富集分析（GSEA）、免疫分析、半数最大抑制浓度（IC50）分析，以及基于NRLs的HCC亚型鉴定。最后，我们在体外检测了 HCC 组织和细胞系中 lncRNA 的表达。结果：共筛选出 508 个 NRL，构建了 7 个 NRL 作为风险分层系统，将患者分为不同的低风险和高风险组。高风险组患者的总生存期（OS）显着低于低风险组患者。使用多变量 Cox 回归分析，我们发现风险评分是 OS 的独立预测因子。功能分析表明，不同患者的免疫状态存在差异。化疗的 IC50 分析表明，高危组患者对常用处方药更敏感。qRT-PCR显示3个高危lncRNA在耐药细胞中表达上调，且在HCC组织中的表达高于癌旁组织。结论：本研究开发的预测特征可用于评估HCC患者的预后和微环境，为HCC治疗选择提供新的基准。