Cuproptosis相关lncRNAs在结直肠癌中的潜在预后价值  

Potential Prognostic Value of Cuproptosis-related lncRNAs in Colorectal Cancer

作　　者：李寅臻 农卫霞[2] 张眉[1] 芮东升[1] 雷伟 摆文丽 李瑞 张亚洲 王奎 LI Yinzhen;NONG Weixia;ZHANG Mei;RUI Dongsheng;LEI Wei;BAI Wenli;LI Rui;ZHANG Yazhou;WANG Kui(Department of Preventive Medicine,Shihezi University School of Medicine,Shihezi 832000,Xinjiang,China;Department of Rheumatology,the First Affiliated Hospital of Shihezi University,Shihezi 832000,Xinjiang,China)

机构地区：[1]石河子大学医学院预防医学系,新疆石河子832000 [2]石河子大学第一附属医院风湿血液科,新疆石河子832000

出　　处：《医学信息》2025年第2期1-13,共13页Journal of Medical Information

基　　金：国家自然科学基金项目(编号:81860374)。

摘　　要：目的探讨与铜死亡(Cuproptosis)相关的lncRNA在结直肠癌(CRC)之间的关系,并构建预后模型来预测CRC的预后。方法通过TCGA数据库下载CRC的转录组数据、基因组数据和临床数据;从已发表的文献中收集Cuproptosis基因,将整理好的转录组数据区分为mRNA和lncRNA,通过共表达分析筛选出与Cuproptosis共表达的lncRNA,并构建预后模型。通过独立预后分析研究模型能否作为独立的预后因子,并分析不同临床分组中高低风险组之间的差异,通过差异分析探索高低风险组之间的差异基因,并进行富集分析,最后分析模型中lncRNA在肿瘤突变负荷,免疫浸润和药物敏感性中的作用。结果构建了一个由5个新的与Cuproptosis相关的lncRNA组成的模型,风险评分=(0.809×LINC01545)+(0.569×AP001160.4)+(0.508×AL442125.2)+(-2.107×AC115989.1)+(-0.280×AC103591.3),其中训练组1、3、5年的曲线下面积分别为:0.732、0.740和0.768;通过PCA图,发现模型可以很好的区分高低风险组患者,并且可以作为独立的预后因素,其中单因素HR=1.119(1.070,1.169),多因素HR=1.077(1.024,1.133);高低风险组在年龄>65岁、男性、女性、Ⅰ~Ⅱ期、T1~T2期、T3~T4期、M0期、N0期和N1期临床分组中的生存状态存在差异(P<0.05)。高低风险组间的12个差异基因主要富集在受体配体活性和动作电位的调节等。低肿瘤突变负荷合并低风险组的患者生存最优,在免疫中,模型中的lncRNA与部分免疫细胞存在相关性,并发现11种药物对高危人群的CRC治疗敏感。结论本次发现了5个新的lncRNA可以很好的预测CRC的预后,并且模型中的lncRNA与CRC的免疫细胞浸润密切相关,发现了11种药物对CRC敏感。Objective To investigate the relationship between lncRNA associated with cuprotosos and colorectal cancer(CRC),and to construct a prognostic model to predict the prognosis of CRC.Methods The transcriptome data,genomic data and clinical data of CRC were downloaded from TCGA database.Cuproptosis genes were collected from published literatures,and the sorted transcriptome data were divided into mRNA and lncRNA.The lncRNA co-expressed with Cuproptosis was screened by co-expression analysis,and a prognostic model was constructed.Independent prognostic analysis was used to study whether the model can be used as an independent prognostic factor,and the differences between high and low risk groups in different clinical groups were analyzed.The differential genes between high and low risk groups were explored through differential analysis,and enrichment analysis was performed.Finally,the role of lncRNA in tumor mutation load,immune infiltration and drug sensitivity was analyzed.Results A model consisting of five new lncRNAs related to Cuproptosis was constructed,and the risk score=(0.809×LINC01545)+(0.569×AP001160.4)+(0.508×AL442125.2)+(-2.107×AC115989.1)+(-0.280×AC103591.3).The area under the curve of the training group for 1,3 and 5 years was 0.732,0.740 and 0.768,respectively.Through the PCA plot,it was found that the model could well distinguish the patients in the high and low risk groups,and could be used as an independent prognostic factor,including single factor HR=1.119(1.070,1.169),multi-factor HR=1.077(1.024,1.133);there were differences in the survival status of the high and low risk groups in the clinical groups of age>65 years,male,female,I-II,T1-T2,T3-T4,M0,N0 and N1(P<0.05).The 12 differential genes between the high and low risk groups were mainly enriched in the regulation of receptor ligand activity and action potential.Patients with low tumor mutation load and low risk group had the best survival.In immunity,lncRNA in the model was correlated with some immune cells,and 11 drugs were found to be sen

关 键 词：铜死亡 Cuproptosis CRC lncRNA 免疫浸润 肿瘤突变负荷 药物敏感性 

分 类 号：R735.3[医药卫生—肿瘤]