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。
An appraisal of pancreatic cancer prognosis,immune infiltration based on cuproptosis-related long noncoding RNA model and forecasting of traditional Chinese medicine
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 immunoinfiltration 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-infiltrating 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 effects 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 efficacy on the mechanism of coppercuproptosis.
CuproptosisLong noncoding RNAPancreatic cancerPrognostic signatureImmuneinfiltrationTraditional Chinese medicine
万方数据
维普
