Smad3与乳腺癌免疫相关基因关系研究

Relationship Analysis between Smad3 and Breast Cancer Immune-related Genes

探索Smad3促进乳腺癌发展的相关蛋白,为乳腺癌临床诊断和免疫治疗提供靶点。从癌症基因组图谱(TCGA)数据库获得乳腺癌病人转录组数据和临床数据;Estimate系统评估肿瘤微环境的基质细胞和免疫细胞,绘制Kaplan-Meier生存曲线,R语言分析得到肿瘤微环境差异基因。Smad3差异基因联合Immport网站免疫差异基因数据筛选Smad3相关免疫差异基因。筛选出的差异基因进行基因本体(GO)富集分析和蛋白互作(PPI)分析。Smad3免疫差异基因与肿瘤微环境差异基因取交集得到两者关联基因;乳腺癌小鼠模型验证Smad3与交集基因的关联性。结果显示,在肿瘤免疫微环境中免疫细胞高低与病人生存时间相关。进一步通过差异基因分析得知Smad3与基质金属蛋白酶9(MMP9)具有关联性;小鼠模型证实磷酸化的Smad3(p-Smad3)含量越高MMP9表达越高,肿瘤生长越快。由此得出结论,Smad3与MMP9在肿瘤微环境中具有极高的关联性,能调控肿瘤免疫环境;抑制Smad3的磷酸化能显著减少MMP9的表达,减缓肿瘤的生长。

The purpose of this paper is to explore the related proteins of Smad3 which promoting the progression of breast cancer,and provides a target for clinical diagnosis and immunotherapy of breast cancer.Transcriptome data and clinical data of breast cancer patients were obtained from TCGA.The stromal cells and immune cells in the tumor microenvironment were evaluated by the Estimate system.And Kaplan-Meier survival curve was plotted combined with immune score and stromal score.The tumor microenvironment differential genes were obtained by R language analysis.The Smad3-related immune differential genes were screened via Smad3 differential genes together with immune differential gene data on Immport website.The screened differential genes were for GO enrichment analysis,and PPI protein interaction analysis.Smad3 immune differential gene and tumor microenvironment differential gene were intersected to obtain their associated genes.The relationship between Smad3 and intersection genes was verified in a mouse model with breast cancer.The results showed that the level of immune cells was significant with the survival rate in tumor immune microenvironment.The differential gene analysis showed that there are high relationship between Smad3 and MMP9.The mouse model verified that higher expression of p-Smad3 was corresponding to higher MMP9,promoting the growth of breast cancer.It can be concluded that Smad3 is so highly correlated with MMP9 in the tumor immune microenvironment that can regulate the expression of MMP9.Inhibiting the phosphorylation of Smad3 could slow down the growth of tumors.