The expression and prognostic impact of CXC-chemokines in stage II and III colorectal cancer epithelial and stromal tissue.
The expression and prognostic impact of CXC-chemokines in stage II and III colorectal cancer epithelial and stromal tissue.
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DOI：
10.1038/sj.bjc.6606055
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发表时间：
2011-02-01
影响因子：
8.8
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中科院分区：
文献类型：
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CXC趋化因子的表达与结直肠癌（CRC）的进展有关，但其在切除的CRC中的意义尚不清楚。我们探讨了这种表达对II期和III期结直肠癌预后的影响。组织微阵列由II期和III期CRC活检组织构建（n=254），通过免疫组化对恶性和邻近正常组织中CXCL 1和CXCL 8及其受体CXCR 1和CXCR 2的表达进行分级，并与预后因素相关。CXCL 1、CXCR 1和CXCR 2在癌组织中的表达均高于癌旁正常组织（P<0.001）。CXCL 8表达在肿瘤周围炎性浸润中可检测到。CXCL 1、CXCR 1或CXCR 2表达与预后终点之间没有总体相关性;然而，单变量亚组生存分析表明，CXCL 1与III期患者的无复发生存期（RFS）呈负相关（P=0.041）。然而，肿瘤浸润中的CXCL 8阳性与早期疾病阶段（P<0.001）和整个队列中改善的无复发生存期（P<0.001）相关。在多变量考克斯回归分析中，疾病分期（P<0.001）和肿瘤浸润CXCL 8阳性（P=0.007）与RFS增强相关。自分泌CXC-趋化因子信号可能对早期CRC的预后有不良影响。相反，免疫浸润内的CXCL 8阳性可能具有良好的预后意义。
The CXC-chemokine expression is linked with colorectal cancer (CRC) progression but their significance in resected CRC is unclear. We explored the prognostic impact of such expression in stage II and III CRC. Tissue microarrays were constructed from stage II and III CRC biopsies (n=254), and the expression of CXCL1 and CXCL8, and their receptors CXCR1 and CXCR2, in malignant and adjacent normal tissue was graded by immunohistochemistry and was correlated with prognostic factors. Expression of CXCL1, CXCR1 and CXCR2 was elevated in tumour epithelium relative to normal adjacent tissue (P<0.001). CXCL8 expression was detectable in the peritumoural inflammatory infiltrate. There was no overall association between CXCL1, CXCR1 or CXCR2 expression and prognostic endpoints; however, univariate subgroup survival analysis demonstrated an inverse association between CXCL1 and recurrence-free survival (RFS) in stage III patients (P=0.041). The CXCL8 positivity in the tumour infiltrate, however, correlated with earlier disease stage (P<0.001) and improved relapse-free survival across the cohort (P<0.001). Disease stage (P<0.001) and tumour infiltrate CXCL8 positivity (P=0.007) were associated with enhanced RFS in multivariate Cox regression analysis. Autocrine CXC-chemokine signalling may have adverse prognostic effects in early CRC. Conversely, CXCL8 positivity within the immune infiltrate may have good prognostic significance.