摘要
目的 探讨老年肝细胞癌(HCC)患者中新型的双硫死亡相关lncRNA(DRLS)预后模型,验证该模型在评价老年HCC患者的预后及指导治疗选择中的应用价值。方法 从癌症基因组图谱(TCGA)下载TCGA-LIHC项目的转录组数据、临床资料及突变信息。筛选DRLS,分为老年组和年轻组。使用韦恩图排除对年轻组HCC有影响的lncRNA,保留仅对老年组有影响的DRLS。通过Cox回归和最小绝对收缩及选择算子(LASSO)分析,构建DRLS预后模型。评估老年HCC患者高风险组与低风险组的预后、生物功能、突变情况以及药物敏感性的差异。结果 本研究采用LASSO和Cox回归方法确定了DRLS,并将患者分为低风险组和高风险组。低风险组患者的总生存期(OS)和无进展生存期(PFS)显著高于高风险组患者。构建具有良好临床适用性的列线图。通过差异基因表达富集分析发现,这些基因在细胞周期、还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活性产生的超氧化物、细胞分裂、细胞骨架运动以及相关代谢活动中显著富集,低风险组在肿瘤免疫功能障碍及排斥(TIDE)评分较低。在药物敏感性分析中,低风险组对索拉非尼、奥沙利铂和伊立替康表现出更高的敏感性;而高风险组对5-氟尿嘧啶、MIRA-1和星形孢菌素更敏感。老年HCC患者中低风险组的预后更好,突变发生率更低,免疫治疗效果更佳,且对抗肿瘤药物的敏感性更高。结论 DRLS在预测老年HCC患者的预后方面表现出良好的效果,并与其生物学功能、突变基因及药物敏感性密切相关,为深入探索双硫死亡与HCC的关系提供新线索。
Objective This study aims to explore a new prognostic model of disulfidptosis-related lncRNA(DRLS)in elderly hepatocellular carcinoma(HCC)patients and validate its application in evaluating patient prognosis and guiding treatment choices.Methods Transcriptome data,clinical information,and mutation details of the cancer genome atlas liver hepatocellular carcinoma(TCGA-LIHC)were downloaded from TCGA.DRLS were screened and categorized into elderly and young groups.Venn diagrams were used to exclude lncRNAs affecting young group HCC,retaining only those impacting the elderly group.A prognostic model related to DRLS was constructed using Cox regression and the least absolute ahrinkage and aelection operator(LASSO)analysis.Differences in prognosis,biological functions,mutation landscapes,and drug sensitivities between high-risk and low-risk groups in elderly HCC patients were assessed.Results Using LASSO and Cox regression methods,this study established DRLS and divided patients into low-risk and high-risk groups.This study showed that patients in the low-risk group had significantly higher overall survival(OS)and progression-free survival(PFS)than those in the high-risk group,and a clinically relevant nomogram was developed.Differential gene expression enrichment analysis revealed significant enrichment of these genes in cell cycle,superoxide produced by nicotinamide adenine dinucleotide phosphate(NADPH)oxidase activity,cell division,cytoskeletal movement,and related metabolic activities.The low-risk group had lower scores for tumor immune dysfunction and exclusion(TIDE).In drug sensitivity analysis,the low-risk group showed higher sensitivity to sorafenib,oxaliplatin,and irinotecan,while the high-risk group was more sensitive to 5-fluorouracil,MIRA-1,and staurosporine.Overall,elderly HCC patients in the low-risk group had better prognosis,lower mutation rates,better response to immunotherapy,and higher sensitivity to anti-tumor drugs.Conclusion DRLS effectively predicts the prognosis of elderly HCC patients and is closely related to their biological functions,mutation genes,and drug sensitivities,providing new insights for further exploring the relationship between disulfidptosis and HCC.
作者
林世钊
林志明
姚向庆
LIN Shizhao;LIN Zhiming;YAO Xiangqing(Department of Hepatobiliary and Pancreatic Surgery,The First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China;Fujian Abdominal Surgery Research Institute,The First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China;National Regional Medical Center,Binhai Campus of the First Affiliated Hospital,Fujian Medical University,Fuzhou 350212,China;Department of Hematology and Oncology,Fuqing City Hospital Affiliated to Fujian Medical University,Fuzhou 350300,China)
出处
《福建医科大学学报》
2024年第4期222-233,共12页
Journal of Fujian Medical University
基金
福建省卫健委科技计划项目(2023QNA039)。
作者简介
林世钊,男,住院医师,医学硕士;通信作者:姚向庆.Email:yxq2080@126.com。
