Bioinformatics identification of CCL8/21 as potential prognostic biomarkers in breast cancer microenvironment.

BACKGROUND Breast cancer is the most common malignancy among females worldwide. The tumor microenvironment usually prevents effective lymphocyte activation and infiltration, and suppresses infiltrating effector cells, leading to a failure of the host to reject the tumor. CC chemokines play a significant role in inflammation and infection. METHODS In our study, we analyzed the expression and survival data of CC chemokines in patients with breast cancer using several bioinformatics analyses tools. RESULTS The mRNA expression of CCL2/3/4/5/7/8/11/17/19/20/22 was remarkably increased while CCL14/21/23/28 was significantly down-regulated in breast cancer tissues compared to normal tissues. Methylation could downregulate expression of CCL2/5/15/17/19/20/22/23/24/25/26/27 in breast cancer. Low expression of CCL3/4/23 was found to be associated with drug resistance in breast cancer. Results from Kaplan-Meier plotter and bcGenExMiner v4.2 demonstrated that breast cancer patients with high CCL8 and low CCL19/21/22 expression were more like to have a worse prognosis. CCL8 expression was significantly upregulated in breast cancer tissues compared to normal tissues. High CCL8 expression was significantly correlated with negative PR, negative ER, positive nodal status, triple-negative breast cancer subtype, basal-like breast cancer subtype, triple-negative & basal-like breast cancer subtype and high grades. CCL21 was down-regulated in breast cancer, while high levels of CCL21 was associated with negative PR, triple-negative subtype, basal-like subtype and low tumor grade. Functional analysis demonstrated that CCL8 and CCL21 were involved in carcinogenesis, tumor immune escape and chemoresistance in breast cancer. CONCLUSIONS Integrative bioinformatics analysis demonstrated CCL8/21 as potential prognostic biomarkers in breast cancer microenvironment.