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CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma
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)...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621872/ https://www.ncbi.nlm.nih.gov/pubmed/26503598 http://dx.doi.org/10.1186/s13046-015-0247-1 |
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author | Li, Li Xu, Li Yan, Jing Zhen, Zuo-Jun Ji, Yong Liu, Chao-Qun Lau, Wan Yee Zheng, Limin Xu, Jing |
author_facet | Li, Li Xu, Li Yan, Jing Zhen, Zuo-Jun Ji, Yong Liu, Chao-Qun Lau, Wan Yee Zheng, Limin Xu, Jing |
author_sort | Li, Li |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-015-0247-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4621872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46218722015-10-28 CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma Li, Li Xu, Li Yan, Jing Zhen, Zuo-Jun Ji, Yong Liu, Chao-Qun Lau, Wan Yee Zheng, Limin Xu, Jing J Exp Clin Cancer Res Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-015-0247-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-26 /pmc/articles/PMC4621872/ /pubmed/26503598 http://dx.doi.org/10.1186/s13046-015-0247-1 Text en © Li et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Li, Li Xu, Li Yan, Jing Zhen, Zuo-Jun Ji, Yong Liu, Chao-Qun Lau, Wan Yee Zheng, Limin Xu, Jing CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma |
title | CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma |
title_full | CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma |
title_fullStr | CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma |
title_full_unstemmed | CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma |
title_short | CXCR2–CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma |
title_sort | cxcr2–cxcl1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621872/ https://www.ncbi.nlm.nih.gov/pubmed/26503598 http://dx.doi.org/10.1186/s13046-015-0247-1 |
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