目的：利用生物信息学方法分析前梯度蛋白2（anterior gradient protein-2，AGR2）在乳腺癌中的表达情况，并分析预测其所涉及的生物学功能及分子信号通路。方法：挖掘Oncomine 和GEPIA数据库中AGR2 在乳腺癌和正常乳腺组织中的表达情况，分析CCLE数据库中AGR2 在乳腺癌细胞系中的表达水平，同时利用HPA数据库分析AGR2 蛋白在正常和乳腺癌组织中的表达水平，并分析其表达与预后关系。Progno Scan 分析AGR2 表达与预后的关系从CCLE下载乳腺癌相关基因芯片并用R语言筛选AGR2 共表达基因，利用GO功能富集分析和KEGG信号通路分析对AGR2 相关共表达基因进行功能注释。结果：Oncomine和GEPIA数据分析显示AGR2 基因在乳腺癌组织中高表达，CCLE数据分析表明AGR2 在乳腺癌细胞系中显著高表达，HPA数据库免疫组化结果显示乳腺癌组织AGR2 蛋白相对于正常乳腺组织高表达；Progno Scan 分析显示AGR2 高表达提示乳腺癌预后不良。利用R软件共筛选出946 个在乳腺癌中同AGR2 共表达的基因，GO功能富集分析显示，共表达基因主要涉及蛋白定位到细胞周围、蛋白定位到细胞膜、细胞连接组装、细胞基质黏附、细胞连接组成等生物学功能；KEGG分析显示共表达基因主要参与乳腺癌和胃癌进程，并和蛋白聚糖在癌症中的作用及缬氨酸、亮氨酸、异亮氨酸降解通路相关。结论：AGR2 在乳腺癌组织和细胞中均高表达，其可能是乳腺癌中潜在的促癌基因，有望成为乳腺癌治疗的新靶标。

Objective: To explore the expression of AGR2 gene in breast cancer as well as to predict its relevant biological functions and molecular signaling pathways with bioinformatics tool. Methods: The expression of AGR2 in breast cancer tissues and normal tissues was analyzed in Oncomine and GEPIA databases, and the expression of AGR2 in breast cancer cell lines was evaluated in CCLE database. Meanwhile, HPA database was used to analyze the expression of AGR2 protein in normal and breast cancer tissues. Besides,the gene expression microarray data download from CCLE database was analyzed by using R software to obtain genes co-expressed with AGR2. Functional annotation of AGR2 co-expressed genes was performed by using GO Enrichment and KEGG pathway analyses.Results: Oncomine and GEPIA databases showed that AGR2 gene was highly expressed in breast cancer tissues, and CCLE database analysis showed that AGR2 was highly expressed in all breast cancer cell lines. Immunohistochemistry results from the HPA database showed that the expression of AGR2 protein was significantly higher in breast cancer tissues compared with normal tissues. A total of 946 genes co-expressed with AGR2 in breast cancer were screened out with the R software. With the GO function Enrichment analysis,the co-expressed genes were demonstrated to be mainly involved in biological functions, such as protein localization to cell periphery,protein localization to plasma membrane, cell junction assembly, cell-substrate adhesion, and cell junction organization etc. In addition,the KEGG analysis results showed that co-expressed genes were mainly involved in the progression of gastric cancer and breast cancer,and were associated with proteoglycans in cancer, as well as proline, leucine and isoleucine degradation pathways. Conclusions: AGR2 is highly expressed in breast cancer tissues, which may be a potential oncogenic gene and a new therapeutic target of breast cancer.

国家自然科学基金资助项目（No. 81372843）