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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2015 | Research

CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma

Authors: Li Li, Li Xu, Jing Yan, Zuo-Jun Zhen, Yong Ji, Chao-Qun Liu, Wan Yee Lau, Limin Zheng, Jing Xu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2015

Abstract

Background & aims

Inflammation is a hallmark of cancer, yet the mechanisms that regulate immune cell infiltration into tumors remain poorly characterized. This study attempted to characterize the composition, distribution, and prognostic value of CXCR2⁺ cells in hepatocellular carcinoma (HCC) and to examine the CXCR2 ligands that are responsible for local immune infiltration in different areas of HCC tumors.

Methods

Immunohistochemistry and immunofluorescene were used to identify CXCR2⁺ cells in HCC tissues. Kaplan–Meier analysis and Cox regression models were applied to estimate recurrence-free survival (RFS) and overall survival (OS) for 259 HCC patients. The expression levels of CXCR2 ligands (CXCL-1, −2, −5, and −8) were measured by real-time PCR and compared with local immune cell density. The combined prognostic value of the CXCR2–CXCL1 axis was further evaluated.

Results

In HCC tissues, CXCR2⁺ cells were mainly neutrophils that were enriched in the peri-tumoral stroma (PS) region. Kaplan–Meier survival analysis showed that increased CXCR2⁺ _PS cells were associated with reduced RFS and OS (P = 0.015 for RFS; P = 0.002 for OS). Multivariate Cox proportional hazards analysis identified CXCR2⁺ _PS cell density as an independent prognostic factor for OS (hazard ratio [HR] = 1.737, 95 % confidence interval [CI] = 1.167–2.585, P = 0.006). Furthermore, we detected a positive correlation between the density of CD15⁺ neutrophils and CXCL1 levels in both the peri-tumoral stroma and intra-tumoral regions. The combination of CXCR2 and CXCL1 expression levels represented a powerful predictor of a poor prognosis for patients with HCC.

Conclusions

Our data showed that the CXCR2⁺ cell density was an independent prognostic factor for predicting OS for HCC patients. The CXCR2–CXCL1 axis can regulate neutrophil infiltration into HCC tumor tissues and might represent a useful target for anti-HCC therapies.

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Title: CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma
Authors: Li Li
Li Xu
Jing Yan
Zuo-Jun Zhen
Yong Ji
Chao-Qun Liu
Wan Yee Lau
Limin Zheng
Jing Xu
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2015
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-015-0247-1

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Abstract

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Conclusions

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