CXCR4/CXCL12 expression profile is associated with tumor microenvironment and clinical outcome of liver metastases of colorectal cancer
CXCR4/CXCL12 expression profile is associated with tumor microenvironment and clinical outcome of liver metastases of colorectal cancer
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DOI：
10.1007/s10585-011-9433-5
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发表时间：
2012-02-01
影响因子：
4
通讯作者：
Miyazaki, Masaru
中科院分区：
文献类型：
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作者：
Sakai, Nozomu;Yoshidome, Hiroyuki;Miyazaki, Masaru
CXCR4和CXCL12之间的相互作用在肿瘤进展中起作用。本研究检测了CXCR4，CXCL12和CD133在结直肠癌肝转移（CLM）中的表达，并确定表达谱是否影响肿瘤微环境，从而影响进展，以及它们是否可以作为生存的预后标志物。收集92例结直肠癌肝转移患者的临床病理资料，采用免疫组化方法检测CXCR4、CXCL12和CD133的表达。在结肠直肠癌细胞系SW48中测定CXCR4的表达谱。36例（39%）患者胞浆CXCR 4表达高于肝细胞CXCR 4染色强度所示。23例（25%）患者的高水平细胞核CXCR4表达与肝细胞中CXCL12表达显著相关。暴露于CXCL12后，癌细胞中的核CXCR4表达增加。单变量和多变量分析表明，肝细胞核CXCR4和CXCL12的高水平表达是CLM患者总体和无肝病生存率的显著更好的预后因素。CXCR4和CXCL12在CLM中的表达可能具有相互作用，从而改变肿瘤微环境。CXCR4在转移性肝肿瘤中的表达以及CXCL12在肝细胞中的上调可能有助于预测肝切除术后CLM患者的临床结局。
Interaction between CXCR4 and CXCL12 plays a role in tumor progression. The present study examined CXCR4, CXCL12 and CD133 expression in liver metastases of colorectal cancer (CLM) and determined whether the expression profiles affect the tumor microenvironment and thus progression, and whether they could serve as a prognostic marker for survival. Liver metastases of colorectal cancer collected from 92 patients were evaluated by CXCR4, CXCL12 and CD133 immunohistochemistry and clinicopathological data were analyzed. The expression profile of CXCR4 was determined in the colorectal cancer cell line, SW48. The expression of cytoplasmic CXCR4 was higher in 36 (39%) patients than that indicated by CXCR4 staining intensity of hepatocytes. High levels of nuclear CXCR4 expression in 23 (25%) patients significantly correlated with CXCL12 expression in hepatocytes. Nuclear CXCR4 expression was increased in the cancer cells after exposure to CXCL12. Univariate and multivariate analyses demonstrated that the high levels of nuclear CXCR4 and CXCL12 expression in hepatocytes were significantly better prognostic factors for overall and hepatic disease-free survival in patients with CLM. The expression of CXCR4 and CXCL12 in CLM may have an interactive effect that could alter the tumor microenvironment. CXCR4 expression in metastatic liver tumors together with the upregulation of CXCL12 in hepatocytes may help to predict the clinical outcomes of patients with CLM after hepatectomy.