肝细胞癌双硫死亡相关lncRNA预后模型构建和功能机制探索
The Construction of Disulfide-related LncRNA Prognostic Model and Exploration of Its Functional Mechanisms in Hepatocellular Carcinoma
刘艺涵 1崔龙 2李欣 3客蕊4
作者信息
- 1. 黑龙江中医药大学,黑龙江哈尔滨 150000
- 2. 齐齐哈尔市中医院肿瘤科,黑龙江齐齐哈尔 161000
- 3. 齐齐哈尔医学院附属四院,黑龙江齐齐哈尔 161000
- 4. 黑龙江中医药大学附属第一医院老年病科,黑龙江哈尔滨 150000
- 折叠
摘要
目的 探索双硫死亡相关长链非编码RNA(lncRNA),进一步构建风险预测模型,以期为肝细胞癌的预后评估及个体化治疗提供新的生物标志物.方法 从TCGA数据平台中下载肝细胞癌转录组数据及临床数据,运用皮尔森相关分析筛选出双硫死亡相关lncRNA.通过多种算法构建预测模型.采用单因素和多因素Cox回归、Kaplan-Meier生存曲线、ROC曲线、DCA决策曲线以及列线图对预后模型进行效能评估和验证.计算每例患者的风险评分,根据评分中位数将患者分为低风险组和高风险组,进行免疫逃逸(TIDE)、免疫检查点、m6A修饰基因相关性分析以及药物敏感性分析,通过基因突变、基因集富集分析(GSEA)对其生物学特征进行评价.结果 本研究共鉴定了 5个双硫死亡相关lncRNAs并据此构建风险预测模型.生存分析显示高风险组患者总生存期显著低于低风险组(P＜0.001).该模型的1、3、5年生存预测AUC值分别为0.773、0.725和0.679.单因素、多因素Cox回归证实了该模型的独立预后价值(P＜0.001).列线图内部验证显示模型预测的可信度较好.高低风险组在免疫逃逸潜能评分、关键免疫检查点和m6A修饰基因表达水平、以及对常用HCC治疗药物的耐药性上均表现出显著差异.结论 本研究构建的双硫死亡相关lncRNAs预后模型具有良好的预测准确性,可作为新的生物标志物,评估HCC患者的生存预后和免疫逃逸倾向,为临床决策提供有价值的参考.
Abstract
Objective This study aimed to investigate long non-coding RNAs(LncRNAs)associated with disulfidptosis and to construct a risk prognostic model using identified LncRNAs,and to further identify novel biomarkers for prognostic assessment and individualized therapy in hepatocellular carcinoma(HCC).Methods Transcriptome and clinical data of HCC were downloaded from TCGA database.We used Pearson correlation analysis to identify LncRNAs linked to disulfidptosis.A risk prognostic model was developed employing multiple algorithmic approaches.Univariate Cox proportional hazards(Cox),multifactorial Cox,Kaplan-Meier(KM)analysis,ROC curves,DCA decision curve analysis,and nomogram method were employed to demonstrate its efficacy.Patients were stratified into low-and high-risk groups based on their risk scores.Subsequently,we conducted TIDE analysis,immune checkpoints analysis,m6A analysis,and drug sensitivity analysis.We then performed Gene Set Enrichment Analysis(GSEA)and gene mutation analysis to evaluate biological characteristics.Results Our study identified five disulfidptosis-associated LncRNAs to develop a prognostic model.Survival analysis indicated a markedly reduced overall survival period in the high-risk group compared to their low-risk counterparts(P＜0.001).The model yielded robust AUC values of 0.773,0.725,and 0.679 for predicting one-year,three-year,and five-year survival,respectively.Both univariate and multivariate Cox regression analyses reinforced the model's independent prognostic validity(P＜0.001).The nomogram demonstrated notable predictive reliability.Significant disparities were observed between the high and low-risk groups,particularly in immune escape,expression levels of immune checkpoint genes and m6A modification genes,and their drug sensitivity.Conclusion The prognostic model based on disulfidptosis-associated LncRNAs exhibits strong predictive accuracy.It offers critical insights into the survival outcomes and immune evasion in HCC,aiding in clinical decision-making.
关键词
肝细胞癌/双硫死亡/长链非编码RNA/预测模型Key words
Hepatocellular carcinoma/Disulfidptosis/Long non-coding RNA/Risk prognostic model引用本文复制引用
基金项目
黑龙江生卫生健康委科技计划项目(202203030906007)
黑龙江省中医药管理局专项课题(ZYW2023-066)
出版年
2024
NETL
NSTL
万方数据