C-C基序趋化因子配体23是乳腺癌的新型预后标志物且与免疫浸润相关

C-C motif chemokine ligand 23 is a novel prognostic marker of breast cancer and related to immune infiltration

目的:基于TCGA和GEO数据开发的多种在线工具探讨C-C基序趋化因子配体23(CCL23)在乳腺癌组织中的表达差异、预后价值和潜在调控机制。方法:采用GEPIA2.0、TIMER和Oncomine数据库联合分析CCL23在乳腺正常组织和乳腺癌组织的表达差异;基于GEPIA2.0和PrognoScan数据库分析CCL23在乳腺癌患者中的预后潜力;采用LinkedOmics与GeneMANIA数据库阐明CCL23参与的生物学行为和蛋白互作网络;TIMER数据库探讨CCL23与肿瘤免疫细胞数的关系。结果:与正常组织比较,乳腺癌组织CCL23 mRNA表达显著下调,高表达CCL23 mRNA的乳腺癌患者OS、DFS、DMFS较好;前50个共表达基因中有18个与患者预后相关;KEGG富集分析提示CCL23及其共表达基因参与乳腺癌免疫调节。乳腺癌组织CCL23 mRNA表达与肿瘤纯度呈显著负相关,与B细胞、CD4^(+)T细胞、CD8^(+)T细胞、巨噬细胞、树突状细胞和中性粒细胞数呈正相关。调节肿瘤纯度后,CCL23与多个CD4^(+)T细胞和CD8^(+)T细胞活化标志物呈显著正相关。结论:CCL23在乳腺癌组织中低表达,且与乳腺癌良好预后有关,具有作为乳腺癌预后潜在标志物的潜能。

Objective:To investigate differential expression,prognostic value and potential regulatory mechanisms of C-C motif chemokine ligand 23(CCL23)in breast cancer tissues based on a variety of online tools containing TCGA and GEO data.Methods:GEPIA2.0,TIMER and Oncomine databases were used to analyze difference of CCL23 expression in normal breast tissues and breast cancer tissues;GEPIA2.0 and PrognoScan databases were used to analyze prognostic potential of CCL23 in breast cancer patients;LinkedOmics and GeneMANIA databases were used to understand biological behavior and interaction protein network involved in CCL23;TIMER database was used to investigate relationship between CCL23 and number of tumor immune cells.Results:Compared with normal tissues,CCL23 mRNA expression was significantly down-regulated in breast cancer tissues,and breast cancer patients with high-expression of CCL23 mRNA had better OS,RFS and DMFS. Eighteen of top 50 co-expressed genes were associated with prognosis of patients;KEGG enrichment analysis suggested that CCL23 and its co-expressed genes were involved in breast cancer immune regulation. CCL23 mRNA expression was also found to be significantly negatively correlated with tumor purity and positively correlated with number of B cells,CD4^(+)T cells,CD8^(+)T cells,macrophages,dendritic cells and neutrophils in breast cancer tissue. There was a significant positive correlation between CCL23 and multiple CD4^(+)T cells and CD8^(+)T cell activation markers by modulating tumor purity.Conclusion:CCL23 is low-expression in breast cancer tissues,and associated with good prognosis of breast cancer patients and has potential to be used as a potential prognosis marker for breast cancer patients.