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Published on: April 13, 2015
[Chemerin mediated neutrophil infiltration in oral squamous cell carcinoma and predicted poor prognosis]
Xiao-Yuan Hu1, Ning Wang, Xiao-Ye Zhang
1Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Qingdao University. Qingdao 266000, Shandong Province, China.
Purpose:
To explore the effect of Chemerin in oral squamous cell carcinoma (OSCC) tissue on neutrophils infiltration and its possible molecular mechanism.
Methods:
The relationship between Chemerin expression and neutrophils density was assessed via double immunohistochemistry staining.The chemotactic effect of Chemerin on neutrophils in OSCC was detected by transwell assay, real-time quantitative PCR(qRT-PCR), Western blot, enzyme-linked immunosorbent assay(ELISA) and flow cytometry. The data were statistically analyzed using SPSS 23.0 software package. The relationship between Chemerin expression and neutrophils density was assessed using Spearman rank correlation analysis. ChemR23 knockout efficiency and chemotactic index were calculated by ANOVA. The relationship between Chemerin expression, neutrophils density and clinicopathological factors was analyzed by Mann-Whitney test. Kaplan-Meier test and Log rank test were used for survival analysis, and risk factors affecting the survival of OSCC patients was assessed using Cox regression model.
Results:
Double immunohistochemistry staining showed that overexpression of Chemerin was significantly correlated with increased neutrophils infiltration in OSCC(P=0.023), and strong Chemerin expression and high neutrophils density were associated with higher clinical stage(P<0.001), cervical lymph node metastasis (P<0.001) and tumor recurrence (P=0.002). Kaplan-Meier survival analysis showed that patients in the strong Chemerin expression + high neutrophils density group had shortened cancer-related overall survival time and disease-free survival time compared with the other two groups. Transwell assay results showed that both OSCC cells and R-Chemerin had a significant chemotactic effect on dHL-60 cells; knockdown of ChemR23 suppressed Chemerin-induced chemotaxis to dHL-60 cells.
Conclusions:
Overexpression of Chemerin in OSCC tissue chemoattracts more neutrophils to tumor sites through its receptor ChemR23 and is related to poor clinical prognosis.
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