C-X-C motif chemokine receptor type 2 correlates with higher disease stages and predicts worse prognosis, and its downregulation enhances chemotherapy sensitivity in triple-negative breast cancer

BACKGROUND: This study aimed to explore the correlation of C-X-C motif chemokine receptor type 2 (CXCR2) expression with tumor stage and overall survival (OS) in triple-negative breast cancer (TNBC) patients, furthermore, to investigate the influence of CXCR2 downregulation on chemotherapy sensitivity in TNBC cells. METHODS: One hundred fifty-eight TNBC patients underwent surgical excision were retrospectively reviewed, and CXCR2 expression in tumor tissue was determined by immunohistochemistry (IHC). In vitro, CXCR2 shRNA and control shRNA were transfected into HCC1937 cells respectively. Doxorubicin and docetaxel with different concentrations were used to treat HCC1937 cells respectively, followed by relative cell viability (%) and IC50 measurements. RESULTS: There were 87 (55.1%) patients presented with CXCR2 high expression, and 71 (44.9%) patients presented with CXCR2 low expression. CXCR2 high expression was positively associated with pathological grade (P=0.007), N stage (P<0.001) and TNM stage (P<0.001), and it predicted unfavorable OS (P<0.001). Further analysis disclosed that CXCR2 high expression independently predicted decreased OS (P=0.028). In vitro, CXCR2 shRNA increased chemosensitivity of HCC1937 cells to doxorubicin and docetaxel, with reduced IC50 concentration of doxorubicin (P<0.05) and docetaxel (P<0.01) compared the control shRNA. CONCLUSIONS: CXCR2 has the potential to serve as a biomarker for assisting TNBC management and prognosis, and targeting CXCR2 provides a novel strategy to circumvent the chemotherapy resistance.