Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55101, Mainz, Germany.
J Cancer Res Clin Oncol. 2011 Jul;137(7):1139-45. doi: 10.1007/s00432-011-0980-6. Epub 2011 Apr 6.
Molecular 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).
Ninety-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.
Human 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).
Thus, CCR5 expression of the primary cancer might be a valuable biomarker indicating the absence of hepatic molecular metastases.
分子转移是术后复发的前兆，可通过分子生物学工具检测到。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 的强烈表达与非转移性结直肠癌和增加的 CD8+T 细胞浸润有关。本研究旨在分析 CCR5 表达是否与肝内分子转移（MM）的存在相关。
评估了 93 例接受结直肠癌择期手术的患者。通过 PCR-RFLP 定义 K-ras 突变状态，并通过 CCR5 特异性逆转录（RT-PCR）分析分析 CCR5 表达状态。术中取肝活检样本筛查 MM。通过 K-ras 特异性 PCR-RFLP 和嵌套 CK20/GCC RT-PCR 检测 MM。将 MM 的患病率与 CCR5 表达状态相关联。
人类结直肠癌中有 53%（密码子 12：47%；密码子 13：6%）存在 K-ras 突变。在 K-ras 突变体中，依赖于所应用的技术（K-ras 特异性 PCR-RFLP 检测与嵌套 CK20/GCC RT-PCR 方法（P=0.004）），在 27-53%的患者中检测到 MM。K-ras 突变体的 CCR5 表达从缺失（23/49：47%）、弱（17/49：35%）、中等（4/49：8%）到强（5/49：10%）不等。通过 K-ras 特异性 PCR-RFLP 检测，在 30%的 CCR5 阴性和 23%的 CCR5 阳性癌症患者中发现 MM。嵌套 CK20/GCC RT-PCR 检测在 87%的 CCR5 阴性和 27%的 CCR5 阳性结直肠癌患者中检测到 MM（P=0.00002）。
因此，原发性癌症的 CCR5 表达可能是一种有价值的生物标志物，表明不存在肝内分子转移。
Zotero 插件