基于铜死亡相关长链非编码RNA模型评估胰腺癌预后、免疫浸润及中药预测  

An appraisal of pancreatic cancer prognosis,immune infi ltration based on cuproptosis-related long noncoding RNA model and forecasting of traditional Chinese medicine

作　　者：孙国栋 蒋婧怡 赵磊[2,4] 蒲唯高 胡继科 何丽娟 贠张君 成慧娟[2] 陈昊[2,3] Sun Guodong;Jiang Jingyi;Zhao Lei;Pu Weigao;Hu Jike;He Lijuan;Yun Zhangjun;Cheng Huijuan;Chen Hao(Public Health Department of Lanzhou University First Hospital,Gansu Lanzhou 730000,China;Key Laboratory of Environmental Oncology of Gansu,Gansu Lanzhou 730030,China;The Second Clinical Medical College of Lanzhou University,Gansu Lanzhou 730030,China;General Surgery Department of The Second Hospital of Lanzhou University,Gansu Lanzhou 730030,China;Hematology and Oncology Department of Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]兰州大学第一医院公共卫生科,甘肃兰州730000 [2]兰州大学第二医院甘肃省环境肿瘤学重点实验室,甘肃兰州730030 [3]兰州大学第二临床医学院,甘肃兰州730030 [4]兰州大学第二医院普外科,甘肃兰州730030 [5]北京中医药大学东直门医院血液肿瘤科,北京100700

出　　处：《临床普外科电子杂志》2024年第2期2-17,共16页Journal of General Surgery for Clinicians(Electronic Version)

基　　金：甘肃省自然科学基金项目(22JR5RA916);甘肃省青年科技基金计划(21JR1RA162);兰州大学第一医院院内基金(ldyyyn2020-46);兰州大学第二医院萃英科技创新项目(2020QN-19)。

摘　　要：目的利用与铜死亡基因有关的长链非编码RNA(cuproptosis-related long noncoding RNA,CRL)构建胰腺癌预后模型,以此预测靶向药物的敏感性,并预测可能调控铜死亡相关基因(cuproptosis-related gene,CRG)的中药。方法采用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库收集183例胰腺癌的RNA序列和临床信息,借助Cox回归、Pearson相关分析、Lasso回归等统计学方法对CRL进行筛查,建立胰腺癌预后的风险模型,通过风险评估和临床属性特征构建诺谟图(Nomogram)。模型的准确性主要采用受试者操作特征曲线(receiver operator characteristic curve,ROC曲线)以及C-指数进行评估。利用风险评分评估免疫浸润和化疗/靶向药的相关性,利用Coremine Medical数据库来预测可能影响CRG的中药。结果基于筛选出的6个CRL(MIR1915HG、PRECSIT、AC004982.1、AC023043.4、AC010999.2、FOXCUT)构建的胰腺癌风险模型,在预测胰腺癌患者1、3、5年生存率时,ROC曲线下面积(area under curve,AUC)分别达到了0.782、0.786、0.912,其预测结果显著优于年龄、Grade分级和TNM分期等指标。风险评分与肿瘤浸润淋巴细胞、调节性T细胞等免疫细胞富集程度及14种化疗/靶向药的敏感性相关。98种中药具有潜在调节CRG的功效,主要以清热解毒、清热泻火为主,归肝、脾、肺经。其中通关藤可能存在对铜死亡机制的关键基因FDX1调控作用。结论以6个CRL构建的风险模型能够评估胰腺癌的预后和免疫情况,通关藤可能在调控铜死亡机制方面发挥重要作用。Objective A prognostic model for pancreatic cancer(PC)based on cuproptosis-related long noncoding RNA(CRL)was constructed to predict the traditional Chinese medicine that regulates cuproptosis-related gene(CRG).Method A risk model for forecasting PC prognosis was constructed by utilizing Cox regression and Pearson correlation analysis,utilizing clinical data and RNA-seqs of 183 PC patients sourced from theTCGA.Screening CRL through LASSO regression,and the nomogram was formed by uniting the risk score and clinical features.To test the model's accuracy,receiver operator characteristic curve(ROC)and C-index were employed.An assessment was made of the correlation between risk scores and immunoinfi ltration and chemotherapy/targeted agents.The potential Chinese medicines for controlling CRG were predicted through the utilization of Coremine Medical database.Result The PC risk model was developed based on the risk scores of six CRLs(MIR1915HG,PRECSIT,AC004982.1,AC023043.4,AC010999.2,FOXCUT).The AUC for forecasting 1-year,3-year and 5-year survival rates in PC patients was 0.782,0.786 and 0.912 respectively,as revealed by the risk model,surpassing age,grade and TNM stage.A relationship was found between the risk score and the enrichment of tumor-infi ltrating lymphocytes,the presence of regulatory T cells,and the sensitivity of fourteen chemotherapeutic/targeted drugs.There are ninety-eight Chinese medicines that potentially regulate CRG;their eff ects primarily involve heat clearing and detoxifying properties attributed mainly to liver spleen and lung meridians.Traditional Chinese medicine Tenacissoside may have potential regulatory effects on key gene FDX1 involved in copper death mechanism.Conclusion A risk signature constructed based on six CRLs could assess the prognosis and immunity of PC,and Tenacissoside may have important regulatory effi cacy on the mechanism of coppercuproptosis.

关 键 词：铜死亡 长链非编码RNA 胰腺癌 预后模型 免疫浸润 中药 

分 类 号：R735.9[医药卫生—肿瘤]