二硫下垂是最近发现的一种非凋亡性程序性细胞死亡形式，其与经典的细胞死亡途径不同。然而，二硫键缺失相关的长非编码 RNA (DRL) 的预后意义及其在肝细胞癌 (HCC) 中的潜在机制在很大程度上仍未得到探索。在这项研究中，我们利用了来自 TCGA 的 HCC 患者的 RNA 测序数据和临床信息数据库。通过表达相关性和预后相关性分析，我们确定了一组表现最佳的长非编码 RNA。随后，通过进行 Lasso 回归分析建立了 5-DRL 预测特征。该特征有效地将患者分为高风险组和低风险组，揭示了生存结果的显着差异。通过单变量和多变量 Cox 回归分析的进一步验证证实，从我们的签名中得出的风险评分可以独立预测 HCC 患者的预后。此外，我们观察到两个风险组之间的免疫细胞浸润和肿瘤突变负荷（TMB）存在显着差异，揭示了免疫相关机制与二硫下垂症之间的潜在联系。值得注意的是，该特征在 HCC 患者的化疗药物敏感性和免疫治疗效果方面也表现出预测价值。最后，我们在细胞和患者水平上进行了实验验证，并成功在 HCC 细胞中诱导了二硫下垂表型。总的来说，这种多方面的方法提供了 HCC 中 DRL 概况的全面概述，最终建立了一个有希望的新型风险特征用于预测 HCC 患者的预后和治疗结果。版权所有 © 2024 Cheng、Cheng、Zhang、Li、Yang、Yuan、Fan 和 Liu。

Disulfidptosis is a recently identified form of non-apoptotic programmed cell death which distinguishes itself from classical cell death pathways. However, the prognostic implications of disulfidptosis-related long non-coding RNAs (DRLs) and their underlying mechanisms in hepatocellular carcinoma (HCC) remain largely unexplored.In this study, we leveraged RNA-sequencing data and clinical information of HCC patients from the TCGA database. Through expression correlation and prognostic correlation analyses, we identified a set of top-performing long non-coding RNAs. Subsequently, a 5-DRLs predictive signature was established by conducting a Lasso regression analysis.This signature effectively stratified patients into high- and low-risk groups, revealing notable differences in survival outcomes. Further validation through univariate and multivariate Cox regression analyses confirmed that the risk score derived from our signature independently predicted the prognosis of HCC patients. Moreover, we observed significant disparities in immune cell infiltration and tumor mutation burden (TMB) between the two risk groups, shedding light on the potential connection between immune-related mechanisms and disulfidptosis. Notably, the signature also exhibited predictive value in the context of chemotherapeutic drug sensitivity and immunotherapy efficacy for HCC patients. Finally, we performed experimental validation at both cellular and patient levels and successfully induced a disulfidptosis phenotype in HCC cells.In general, this multifaceted approach provides a comprehensive overview of DRLs profiles in HCC, culminating in the establishment of a novel risk signature that holds promise for predicting prognosis and therapy outcomes of HCC patients.Copyright © 2024 Zheng, Cheng, Zhuang, Li, Yang, Yuan, Fan and Liu.