CXCR2-CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma.
CXCR2-CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma.
复制标题
CXCR2→CXCL1轴与中性粒细胞浸润相关并预测肝细胞癌的不良预后
DOI：
10.1186/s13046-015-0247-1
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发表时间：
2015-10-26
期刊：
影响因子：
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通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Li L;Xu L;Yan J;Zhen ZJ;Ji Y;Liu CQ;Lau WY;Zheng L;Xu J
背景与目标炎症是癌症的一个标志，但调节免疫细胞浸润到肿瘤的机制仍知之甚少。本研究试图表征肝细胞癌（HCC）中CXCR2+细胞的组成、分布和预后价值，并检查负责HCC肿瘤不同区域局部免疫浸润的CXCR2配体。方法采用免疫组织化学和免疫荧光技术鉴定HCC组织中的CXCR2+细胞。应用 Kaplan-Meier 分析和 Cox 回归模型来估计 259 名 HCC 患者的无复发生存期 (RFS) 和总生存期 (OS)。通过实时PCR测量CXCR2配体（CXCL-1、-2、-5和-8）的表达水平，并与局部免疫细胞密度进行比较。进一步评估CXCR2-CXCL1轴的联合预后价值。结果在HCC组织中，CXCR2+细胞主要是中性粒细胞，富集于肿瘤周围基质（PS）区域。 Kaplan-Meier 生存分析表明，CXCR2+PS 细胞的增加与 RFS 和 OS 降低相关（RFS 的 P= 0.015；OS 的 P= 0.002）。多变量 Cox 比例风险分析将 CXCR2+PScell 密度确定为 OS 的独立预后因素（风险比 [HR] = 1.737，95% 置信区间 [CI] = 1.167–2.585，P= 0.006）。此外，我们检测到肿瘤周围基质和肿瘤内区域的 CD15+ 中性粒细胞密度与 CXCL1 水平呈正相关。 CXCR2 和 CXCL1 表达水平的组合代表了 HCC 患者不良预后的有力预测因子。结论我们的数据表明 CXCR2+ 细胞密度是预测 HCC 患者 OS 的独立预后因素。 CXCR2-CXCL1 轴可以调节中性粒细胞浸润 HCC 肿瘤组织，可能是抗 HCC 治疗的有用靶点。
Background & aimsInflammation 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.MethodsImmunohistochemistry 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.ResultsIn 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+PScells were associated with reduced RFS and OS (P= 0.015 for RFS;P= 0.002 for OS). Multivariate Cox proportional hazards analysis identified CXCR2+PScell 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.ConclusionsOur 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.