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结直肠癌与铜死亡相关基因的相关性研究

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目的 探讨结直肠癌(colorectal cancer,CRC)与新型铜死亡相关生物标志物的相关性,为治疗CRC患者预后提供理论支持.方法 在研究中,CRC患者的LncRNA表达谱、临床数据以及突变数据下载来自癌症基因组图谱(TC-GA)CRC数据库,使用R4.1.1软件筛选出与铜死亡相关LncRNA,通过单因素Cox回归分析得到与CRC预后相关的铜死亡LncRNA,采用LASSO Cox回归及交叉验证及多因素Cox分析得出的最显著的LncRNA构建最优预后模型.根据得到的风险评分,将纳入的结直肠癌患者划分为高风险组和低风险组.对构建的模型进行Kaplan-Meier进行生存(OS)及无进展生存期差异分析.同时建立ROC曲线对模型进行验证并建立临床分组验证.随后对差异基因进行基因本体论(GO)、京都基因和基因组百科全书(KEGG)分析.我们还计算了泛癌数据中TMB状态与基因表达之间的相关性,筛选出对CRC治疗的敏感药物.结果 获得36个铜死亡预后相关的LncRNA,且使用LASSO Cox回归及交叉验证及多变量Cox分析从上述36个具有预后意义的铜死亡相关的LncRNA中筛选出17个显著相关的LncRNA(DEGs).接着使用Kaplan-Meier生存分析、无进展生存期及风险差异分析,证明高低风险组是有差异的(P<0.05),ROC曲线显示该预后模型曲线下面积在1年内为0.749,2年内为0.705,3年内为0.710.GO分析结果显示这些交集基因在生物过程主要富集于细胞二价无机阳离子同源等,细胞成分主要富集在含胶原蛋白的细胞外基质,在分子功能主要富集在受体配体a等.KEGG提示主要富集在细胞因子-细胞因子受体相互作用和吞噬体等通路.肿瘤突变负荷的生存分析和药物敏感性是有差异的.结论 通过生物信息学方法,构建了 17个与铜死亡相关基因的预后模型,可能奠定了结直肠癌患者的个体化治疗和评估的基础.
Correlation between Colorectal Cancer and Cuproptosis-Related Genes
Objective In order to explore the biomarkers associated with the cuproptosis in colorectal cancer(CRC);to explore the targeting of cuproptosis to cancer cells,to develop new treatment strategies,which make the foundation for improving the prog-nosis of patients with CRC.Methods In this study,the LncRNA expression profile,clinical data,and mutation data of CRC pa-tients were downloaded from the Cancer Genome Atlas(TCGA)CRC database,and the LncRNA associated with cuproptosis were screened out using R4.1.1 software,the cuproptosis LncRNA associated with CRC prognosis were obtained by univariate Cox regression analysis,and the most significant LncRNA obtained from LASSO Cox regression and cross-validation and multi-variate Cox analysis were used to construct the optimal prognosis model.Based on the risk scores obtained,the included colorec-tal cancer patients were divided into high-risk and low-risk groups.Kaplan?Meier performed a difference analysis of survival(OS)and progression-free survival on the constructed model.At the same time,the ROC curve is established to verify the model and the clinical group verification is established.Differential genes were then analyzed for gene ontology(GO)and Kyoto Gene and Genome Encyclopedia(KEGG)enrichment.We calculated the correlation between TMB status and gene expression in pan-cancer data and screened for drugs sensitive to CRC treatment.Results Thirty-six LncRNA associated with cuproptosis prognosis were obtained,and 17 significantly related LncRNA were screened from the above 36 cuproptosis LncRNA with prog-nostic significance using LASSO Cox regression and cross-validation and multivariate Cox analysis.Then Kaplan-Meier surviv-al analysis,progression-free survival,and risk difference analysis were used to show that there were differences between high and low risk groups(P<0.05),and the ROC curve showed that the area under the prognostic model curve was 0.749 in 1 year,0.705 in 2 years,and 0.710 in 3 years.The results of GO analysis showed that these differential genes were mainly enriched in cell divalent inorganic cation homology,etc.in biological processes,the cellular components were mainly enriched in the colla-gen-containing extracellular matrix,the molecular function was mainly enriched in the receptor ligand a and the like.KEGG suggests that differential genes are mainly enriched in cytokine-cytokine receptor interactions and phagosomes.There are differ-ences in survival analysis and drug sensitivity.Conclusions 17 prognostic models of genes associated with cuproptosis were con-structed Through biological methods,which may provide a reference for the individualized treatment and evaluation of colorectal cancer patients.

colorectal cancerTCGAcuproptosisprognostic modeltumor mutationpotential drug options

周玲、唐梅文、谢佳涛、陈文隆、钟丰羽、许琦、古文姝

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广西中医药大学,广西南宁 530001

广西中医药大学第一附属医院,广西南宁 530023

结直肠癌 TCGA 铜死亡 预后模型 肿瘤突变 潜在药物选择

国家自然科学基金

82060834

2024

实用中医内科杂志
辽宁省中医药学会,中华中医药学会,辽宁省中医药研究院

实用中医内科杂志

影响因子:0.421
ISSN:1671-7813
年,卷(期):2024.38(1)
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