Abstract
Background: Breast cancer (BC) 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 BC 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 BC tissues compared with normal tissues. Methylation could down-regulate expression of CCL2/5/15/17/19/20/22/23/24/25/26/27 in BC. Low expression of CCL3/4/23 was found to be associated with drug resistance in BC. Results from Kaplan–Meier plotter and BC Gene-Expression Miner v4.2 (bcGenExMiner) v4.2 demonstrated that BC patients with high CCL8 and low CCL19/21/22 expression were more likely to have a worse prognosis. CCL8 expression was significantly up-regulated in BC tissues compared with normal tissues. High CCL8 expression was significantly correlated with negative PR, negative ER, positive nodal status, triple-negative BC subtype, basal-like BC subtype, triple-negative and basal-like BC subtype and high grades. CCL21 was down-regulated in BC, 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 BC.Conclusion: Integrative bioinformatics analysis demonstrated CCL8/21 as potential prognostic biomarkers in BC microenvironment.
Highlights
Breast cancer (BC) is the most common malignancy among females worldwide
CCL8 expression was significantly up-regulated in BC tissues compared with normal tissues
Functional analysis demonstrated that CCL8 and CCL21 were involved in carcinogenesis, tumor immune escape and chemoresistance in BC
Summary
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. 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 BC tissues compared with normal tissues. Results from Kaplan–Meier plotter and BC Gene-Expression Miner v4.2 (bcGenExMiner) v4.2 demonstrated that BC patients with high CCL8 and low CCL19/21/22 expression were more likely to have a worse prognosis. CCL8 expression was significantly up-regulated in BC tissues compared with normal tissues. CCL21 was down-regulated in BC, while high levels of CCL21 was associated with negative PR, triple-negative subtype, basal-like subtype and low tumor grade. Stromal cells, inflammatory cells, vasculature and extracellular matrices, usually prevents effective lymphocyte activation and infiltration, and suppresses infiltrating effector cells, leading to a failure of the host to reject the tumor [4]. It is urgent and significant to identify novel immune biomarkers for BC in order to develop individualized treatment plans for patients
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