与二硫酸二硫代肌相关的LNCRNA签名，用于分析肝细胞癌中的肿瘤微环境和临床预后
A disulfidptosis-related lncRNA signature for analyzing tumor microenvironment and clinical prognosis in hepatocellular carcinoma
影响因子:5.90000
分区:医学2区 / 免疫学2区
发表日期:2024
作者:
Haishui Zheng, Jigan Cheng, Ziyun Zhuang, Duguang Li, Jing Yang, Fan Yuan, Xiaoxiao Fan, Xiaolong Liu
摘要
二硫代基因是最近确定的非凋亡程序性细胞死亡的形式，它与经典的细胞死亡途径区分开来。然而，二硫酸二硫代虫相关长的非编码RNA（DRL）及其在肝细胞癌（HCC）中的潜在机制的预后意义仍然在很大程度上无法探索。在这项研究中，我们利用了TCGA数据持续数据持续的RNA续订数据和HCC患者的临床信息。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好的长期非编码RNA。随后，通过进行LASSO回归分析来建立5-DRLS预测性签名。该签名有效地将患者分层为高风险组，揭示了生存结果的显着差异。通过单变量和多元COX回归分析进行进一步验证，证实，我们签名的风险评分独立地预测了HCC患者的预后。此外，我们观察到两个风险群体之间的免疫细胞浸润和肿瘤突变负担（TMB）的显着差异，从而阐明了免疫相关机制与二硫代基因之间的潜在联系。值得注意的是，在化学治疗性药物敏感性和免疫疗法的疗效的背景下，该签名也表现出预测价值。最后，我们在细胞和患者水平上进行了实验验证，并成功诱导了HCC细胞中的二硫代虫表型。总的来说，这种多方面的方法提供了对HCC中DRLS曲线的全面概述，最终导致建立新型风险签名，以预测HCC患者的预测和治疗患者的预测。
Abstract
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.