双硫死亡相关LncRNA的胃癌预后模型构建与验证  

Construction and validation of a gastric cancer prognosis model based on disulfidptosis-related LncRNAs

作　　者：凤亮 曹志国[2] 石小琪 张启坤 陈昌裕[1] 余昌俊[1] Feng Liang;Cao Zhiguo;Shi Xiaoqi;Zhang Qikun;Chen Changyu;Yu Changjun(Dept of Gastrointestinal Surgery,Anhui Medical University,Hefei 230022;Dept of Vascular Surgery,Affiliated Hospital of West Anhui Health Vocational College,Lu'an 237010;Dept of Radiation Oncology,Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院胃肠外科,合肥230022 [2]皖西卫生职业学院附属医院血管外科,六安237010 [3]安徽医科大学第一附属医院放射肿瘤科,合肥230022

出　　处：《安徽医科大学学报》2024年第8期1429-1439,共11页Acta Universitatis Medicinalis Anhui

基　　金：安徽省转化医学研究院科研基金(编号:2022zhyx-C69);安徽高等学校自然科学研究项目(编号:2022AH051174、KJ2021ZD0025、KJ2021A1363);安徽省高校学科(专业)拔尖人才学术资助项目(编号:gxbjZD2022125)。

摘　　要：目的 基于二硫化物应激导致的新型细胞死亡类型,探究与其相关的长链非编码RNA(LncRNA)在胃癌中的作用,建立双硫死亡相关的胃癌预后模型,为胃癌治疗的预后情况评估提供新的方式。方法 使用公开数据库TCGA获得胃癌与正常组织样本的转录组数据,并通过Pearson分析与LASSO-Cox回归分析挑选双硫死亡相关LncRNA。基于上述LncRNA构建出相关的胃癌预后模型,并通过功能富集分析、肿瘤微环境和免疫细胞浸润分析、药物敏感性分析、定量逆转录PCR(RT-qPCR)等进行验证。结果 本研究识别出400个双硫死亡相关的LncRNA,并筛选出其中5个构建预后模型,用于评估胃癌患者的预后情况。模型在验证中显示,高风险评分组的生存期明显短于低风险评分组(P<0.05)。此外,预后模型的预测能力(AUC=0.725)优于仅依据年龄和性别等基本特征进行预测。双硫死亡相关LncRNA在正常组织与胃癌组织中的表达水平存在显著差异(P<0.001)。结论 该研究构建的双硫死亡相关LncRNA预后模型可以用于评估胃癌患者的预后情况和肿瘤微环境,为胃癌新的免疫治疗策略提供潜在的靶点和理论基础。Objective Based on a novel type of cell death induced by disulfide stress,known as disulfidptosis,this study explores the role of long non-coding RNA(LncRNA)in gastric cancer and establishes a prognosis model related to disulfidptosis,providing a new method for assessing the prognosis of gastric cancer treatment.Methods Transcriptomic data from gastric cancer and normal tissue samples were obtained from the public database TCGA,and disulfidptosis-related LncRNAs were selected through Pearson analysis and LASSO-Cox regression analysis.A relevant prognostic model for gastric cancer was constructed based on the above LncRNAs and validated by functional enrichment analysis,tumour microenvironment and immune cell infiltration analysis,drug sensitivity analysis and quantitative reverse transcription PCR(RT-qPCR).Results In this study,400 disulfide death-associated LncRNAs were identified and five of them were screened to construct a prognostic model for assessing the prognosis of gastric cancer patients.The models showed in validation that the survival of the high-risk score group was shorter than that of the low-risk score group(P<0.05).In addition,the predictive ability of the prognostic model(AUC=0.725)was better than that based only on basic characteristics such as age and gender.The expression levels of disulfide death-associated LncRNAs differed between normal and gastric cancer tissues(P<0.001).Conclusion The disulfidptosis-related LncRNA prognosis model developed in this study can effectively assess the prognosis of gastric cancer patients and the tumor microenvironment,providing potential targets and a theoretical basis for new immunotherapeutic strategies for gastric cancer.

关 键 词：长链非编码RNA 细胞死亡 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]