Expression of chemokine receptor CCR5 correlates with the presence of hepatic molecular metastases in K-ras positive human colorectal cancer
Expression of chemokine receptor CCR5 correlates with the presence of hepatic molecular metastases in K-ras positive human colorectal cancer
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DOI：
10.1007/s00432-011-0980-6
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发表时间：
2011-04
影响因子：
3.6
通讯作者：
C. Schimanski;M. Moehler;I. Gockel;T. Zimmermann;H. Lang;P. Galle;M. Berger
中科院分区：
文献类型：
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作者：
C. Schimanski;M. Moehler;I. Gockel;T. Zimmermann;H. Lang;P. Galle;M. Berger
背景分子转移是术后复发的先兆，通过分子生物学手段进行检测。趋化因子及其受体有助于扩散和局部免疫识别。趋化因子受体CCR5的强表达与非转移性结直肠癌和CD8+T细胞浸润增加有关。本研究的目的是分析CCR5的表达是否与肝分子转移(MM)的存在相关。用聚合酶链式反应-限制性片段长度多态性分析检测K-ras基因突变状态，用CCR5特异性逆转录(RT-PCR)分析CCR5基因表达状态。术中取肝活检标本进行MM筛查，采用K-ras特异性聚合酶链式反应-限制性片段长度多态性和巢式CK20/GCC RT-PCR检测MM。结果53%的结直肠癌组织中存在K-ras基因突变(密码子12：47%；密码子13：6%)。在K-ras突变中，27-53%的患者可检测到MM，这取决于所采用的技术(K-ras特异性聚合酶链式反应/限制性片段长度多态性分析与嵌套式CK20/GCC逆转录聚合酶链式反应方法(P=0.004))。K-ras突变体CCR5表达缺失(23/49：47%)、弱(17/49：35%)、中等(4/49：8%)、强(5/49：10%)。K-ras特异性聚合酶链式反应-限制性片段长度多态性分析显示，30%的CCR5阴性患者和23%的CCR5阳性患者存在MM。结论CCR5在结直肠癌组织中的表达可作为判断肝细胞无转移的标志物。结论CCR5在结直肠癌组织中的表达可能是一项有价值的标志物。
BackgroundMolecular metastases are precursors of postoperative recurrence, detected by molecular-biological tools. Chemokines and their receptors contribute to dissemination and local immune recognition. A strong expression of the chemokine receptor CCR5 is associated with non-metastatic colorectal cancer and increased CD8+ T-cell infiltration. The aim of this study was to analyze whether CCR5 expression correlates with the presence of hepatic molecular metastases (MM).MethodsNinety-three patients undergoing elective surgery for colorectal cancer were assessed. The K-ras mutation status was defined by PCR–RFLP, and the CCR5 expression status was analyzed by CCR5-specific reverse transcription (RT-PCR) analysis. Liver biopsy samples had been intra-operatively taken to screen for MM. MM were detected by K-ras-specific PCR–RFLP and nested CK20/GCC RT-PCR. Prevalence of MM was correlated with CCR5 expression status.ResultsHuman colorectal cancer harboured K-ras mutations in 53% (codon 12: 47%; codon 13: 6%) of cases. Among K-ras mutants, MM were detected in 27–53% of patients, dependent on the technique applied (K-ras-specific PCR–RFLP assay vs. nested CK20/GCC RT-PCR approach (P= 0.004)). CCR5 expression of K-ras mutants ranged from absent (23/49: 47%), weak (17/49: 35%), intermediate (4/49: 8%) to strong (5/49: 10%). MM were found in 30% of CCR5 negative and in 23% of CCR5 positive cancer patients by the K-ras-specific PCR–RFLP assay. The nested CK20/GCC RT-PCR assay detected MM in 87% of CCR5 negative and in 27% of CCR5 positive colorectal cancer patients (P= 0.00002).ConclusionThus, CCR5 expression of the primary cancer might be a valuable biomarker indicating the absence of hepatic molecular metastases.