【摘要】 目的 筛选三阴性乳腺癌(triple-negative breast cancer, TNBC)预后相关基因，并探讨影响TNBC预后的可能机制。方法 GEO和TCGA数据库下载表达谱数据，分别使用GEO2R和R语言程序包筛选TNBC和非三阴性乳腺癌差异基因；GO和KEGG富集分析差异基因的分子功能及信号通路；生存曲线和单变量Cox回归分析筛选预后相关基因，ROC曲线进一步验证；Cibersort算法探讨预后相关基因与免疫细胞浸润的关系；HPA数据库在线分析预后相关基因在正常乳腺组织中的分布。结果 获得TNBC差异基因217个，富集在雌激素相关信号通路，生物过程主要富集在乳腺上皮发育、腺体发育、腺体形态发生等，细胞成分主要富集在微绒毛膜、细胞基底外侧膜等，分子功能主要富集于跨膜受体蛋白酪氨酸激酶活性等；筛选出7个预后相关基因，ROC曲线显示AUC值>0.8的有COL9A3;免疫浸润分析显示COL9A3表达与记忆B细胞和单核细胞的浸润程度呈负相关，与初始B细胞和中性粒细胞的浸润程度呈正相关。单细胞测序结果显示COL9A3主要分布在成纤维细胞中。结论 筛选出COL9A3可能作为TNBC预后相关基因；TNBC的发生发展可能与雌激素受体相关信号通路、细胞基底外侧膜和基膜的改变以及单核细胞、中性粒细胞的浸润及EMT的进程有关，为TNBC临床治疗提供参考。更多还原

【Abstract】 Objective To screen three negative breast cancer(TNBC) prognostic related genes by bioinformatics, and explore the possible mechanism.Methods GEO and TCGA databases were used to download expression profile data, and GEO2R and R language packages were used to screen TNBC and non-triple negative breast cancer differential genes, respectively.GO and KEGG enrichment analysis of the molecular functions and signaling pathways of differential genes.Survival curve and univariate Cox regression analysis were used to screen prognostic related genes, and the ROC curve was further validated.The Cibersort algorithm explores the relationship between prognosis related genes and immune cell infiltration.The HPA database analyzes the distribution of prognostic related genes in normal breast tissue online.Results 217 TNBC differential genes were obtained, which were enriched in estrogen related signaling pathways.Biological processes were mainly enriched in mammary epithelial development, glandular development, and glandular morphogenesis.Cell components were mainly enriched in microvilli, cell basement membranes, and molecular functions were mainly enriched in transmembrane receptor protein tyrosine kinase activity.Seven prognostic related genes were screened, and the ROC curve showed that COL9A3 had an AUC value>0.8.The immune infiltration analysis showed that the expression of COL9A3 was negatively correlated with the infiltration of memory B cell and monocytes, and positively correlated with the infiltration of initial B cells and neutrophils.The results of single cell RNA sequencing(ScRNA seq) showed that COL9A3 was mainly distributed in fibroblasts.Conclusion COL9A3 may be selected as a prognostic related gene for TNBC;The occurrence and development of TNBC may be related to estrogen receptor related signaling pathways, changes in cell basement membrane and basement membrane, infiltration of monocytes and neutrophils, and the progression of EMT,providing reference for clinical treatment of TNBC.更多还原