趋化因子受体3对乳腺癌调控机制的探究及其临床意义

The exploration and clinical significance of chemokine receptor 3 in breast cancer regulation mechanism

目的研究趋化因子受体3(CCR3)在乳腺癌组织中的表达情况,并分析嗜酸性粒细胞(EOS)在CCR3对乳腺癌调控中的作用。方法通过癌症基因组图谱(TCGA)数据库分析61例乳腺癌患者乳腺癌组织及其癌旁组织中CCR3的表达情况;检测50例乳腺癌患者(乳腺癌组)和50例健康体检者(对照组)外周血中EOS的计数及及其所占白细胞比例;运用基因集合富集分析(GSEA)法分析CCR3与乳腺癌细胞增殖和转移的关系;通过GEO数据库选取914例乳腺癌患者的乳腺癌基因芯片数据分析CCR3与乳腺癌患者预后的关系。结果乳腺癌组织中CCR3的表达水平明显高于癌旁组织(P<0.01)。乳腺癌患者外周血中EOS的计数及其所占白细胞比例中位水平均明显低于对照组(P<0.01)。基因富集分析结果显示,CCR3的表达与乳腺癌细胞的增殖和转移呈正相关。CCR3低、中、高表达患者的无复发生存(RFS)比较,CCR3高表达患者的RFS情况更优(P<0.01)。结论CCR3可能通过调节EOS促进乳腺癌细胞的增殖和转移,且CCR3与乳腺癌患者的无复发生存情况有关。

Objective To investigate the expression of chemokine receptor 3 (CCR3) in breast cancer tissues, and to explore the role of eosinophils (EOS) in the regulation of breast cancer by CCR3. Method The Cancer Genome Atlas (TCGA) database was used to analyze the expression of CCR3 in breast cancer tissues and paired adjacent normal tissues of 61 breast cancer patients. EOS count and proportion in peripheral blood were measured in 50 patients with breast cancer (breast cancer group) and 50 healthy subjects (control group). The relationship between CCR3 and breast cancer proliferation and metastasis was analyzed by gene set enrichment analysis (GSEA). Breast cancer gene chip data of 914 patients with breast cancer were selected from the gene expression omnibus (GEO) database to analyze the relationship between the expression of CCR3 and the prognosis of breast cancer. Result The expression level of CCR3 in breast cancer tissues was significantly higher than that in adjacent tissues (P<0.01). EOS counts in peripheral blood of breast cancer patients and the median level of the proportion of white blood cells in EOS were both significantly lower than those in the control group (P<0.01). Bioinformatics analysis showed the high expression of CCR3 was positively correlated with the proliferation and metastasis of breast cancer cells (P<0.01). Conclusion CCR3 might promote the proliferation and metastasis of breast cancer through regulating EOS, and CCR3 was associated with recurrence-free survival in breast cancer patients.