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). , 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.