结肠癌肝转移与肺转移关键基因集筛选及功能分析  

Screening and Functional Analysis of Key Genes Involved in Liver and Lung Metastasis of Colon Cancer

作　　者：甘国容 罗莉[1] 罗丽娜[1] 王永祥 李俊 Gan Guorong;Luo Li;Luo Lina(The First People′s Hospital of Zigong City,Zigong,Sichuan 643000,China)

机构地区：[1]自贡市第一人民医院,四川自贡643000 [2]中南大学湘雅医学院,湖南长沙410000

出　　处：《四川医学》2024年第7期726-733,共8页Sichuan Medical Journal

摘　　要：目的挖掘结肠癌转移的关键基因及其临床意义。方法基于TCGA和GEO(GSE41258)中的结肠癌数据集,利用WGCNA包和Limma包分析结肠癌转移相关的基因集,并分析基因集对预后及肿瘤临床分其的影响。随后利用Metascape构建每一个关键基因的蛋白互作网络,并利用DAVID根据蛋白互作网络进行功能富集分析。最后,利用TIDE数据库,从免疫角度分析关键基因对细胞毒性T细胞的免疫浸润以及免疫应答的影响。结果本研究筛选出了CNN1、CXCL10、CXCL11、MGP、SPINK4和PBK 6个关键基因,不仅影响患者预后,同时与结肠癌的肿瘤分期呈现线性关系。通过KEGG与GO富集发现结肠癌肝转移关键基因网络调控细胞因子功能、中心粒细胞驱化以及单核细胞驱化等免疫过程,而在结肠癌肺转移关键基因网络调控RAS信号通路,这些结果揭示了结肠癌不同转移途径的机制差异。其中,CNN1、MGP抑制细胞毒性T细胞的免疫应答,PBK促进细胞毒性T细胞的免疫应答。结论CNN1、CXCL10、CXCL11、MGP、SPINK4和PBK 6个基因可以作为结肠癌转移的筛查分子标志物,并在结肠癌的免疫治疗中发挥作用,为潜在的结肠癌的治疗靶标。Objective To identify key genes associated with metastasis in colon cancer and their clinical significance.Methods Based on colon cancer datasets from TCGA and GEO(GSE41258),we used the WGCNA and Limma packages to analyze gene sets related to colon cancer metastasis,and studied the impact of these gene sets on prognosis and clinical tumor staging,with statistically significant genes identified as key genes.Subsequently,using Metascape,we constructed protein interaction networks for each key gene,and performed functional enrichment analysis on these networks with DAVID.Lastly,by utilizing the TIDE database,we analyzed the influence of key genes on immune infiltration by cytotoxic T cells and the immune response from an immunological perspective.Results The study identified six key genes:CNN1,CXCL10,CXCL11,MGP,SPINK4,and PBK,which not only affected patient prognosis but also showed a linear relationship with the stages of colon cancer.Through KEGG and GO enrichment analysis,it was found that the key gene networks regulating the immune processes such as cytokine activity,chemotaxis of centriole cells,and chemotaxis of monocytes were implicated in liver metastasis of colon cancer,while in lung metastasis,the DAVID RAS signaling pathway was indicated.These results revealed the mechanistic differences in different metastatic pathways of colon cancer.Among them,CNN1 and MGP suppressed the immune response of cytotoxic T cells,while PBK promoted it.Conclusion The six genes,CNN1,CXCL10,CXCL11,MGP,SPINK4,and PBK,can serve as molecular biomarkers for the screening of colon cancer metastasis and play a role in the immunotherapy of colon cancer,presenting potential therapeutic targets for treatment.

关 键 词：结肠癌肝转移 结肠癌肺转移 预后 免疫 

分 类 号：R735.35[医药卫生—肿瘤]