基质细胞衍生因子-1α（SDF-1α）G801A多态性可预测T3期结直肠癌的淋巴结转移。

SDF-1alpha G801A polymorphism predicts lymph node metastasis in stage T3 colorectal cancer.

作者信息

Chang Shih-Ching, Lin Pei-Ching, Yang Shung-Haur, Wang Huann-Sheng, Li Anna Fen-Yau, Lin Jen-Kou

机构信息

Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.

出版信息

Ann Surg Oncol. 2009 Aug;16(8):2323-30. doi: 10.1245/s10434-009-0501-x. Epub 2009 May 27.

DOI:10.1245/s10434-009-0501-x

PMID:19472013

Abstract

BACKGROUND

The SDF-1/CXCR4 axis plays an important role in cancer metastasis. SDF1alpha genetic polymorphisms, including SDF1alpha-G801A, have been associated with increased cancer risk and may be predictive of distant metastasis. The present study compared the frequency of 6 SDF1alpha single-nucleotide polymorphisms (SNPs) in patients with colorectal cancer (CRC) with and without lymph node (LN) metastasis and determined whether fibroblasts with different SDF-1alpha genotypes influenced cancer cell proliferation and migration.

METHODS

The study enrolled 424 patients with primary T3 stage CRC, with and without lymph node metastasis, and a median follow-up of 48 months. The polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to identify polymorphisms. Fibroblasts were harvested from 14 patients with stage II CRC and fibroblast-mediated enhancement of cancer cell proliferation and migration was evaluated.

RESULTS

Only the SDF1alpha-G801A polymorphism was associated with LN metastasis. The frequency of GA/AA genotypes was significantly higher in patients with LN metastasis (54.8%) than in patients without LN metastasis (40.7%). In the latter group, disease-free survival was shorter in patients with the GA/AA genotype (74%) than in patients with the GG genotype (87.6%). In patients with LN metastasis, disease-free survival was similar regardless of genotype. Expression of SDF-1alpha mRNA in GA/AA fibroblasts was three times that in GG fibroblasts. GA/AA (but not GG) fibroblasts enhanced colon cancer cell (HCT116) proliferation and migration. These effects were blocked by an SDF-1alpha neutralizing antibody.

CONCLUSIONS

The SDF1alpha-G801A polymorphism may increase expression of SDF-1alpha mRNA and be a predictive marker of lymph node metastasis in colorectal cancer.

摘要

背景

基质细胞衍生因子-1（SDF-1）/CXC趋化因子受体4（CXCR4）轴在癌症转移中起重要作用。SDF1α基因多态性，包括SDF1α-G801A，与癌症风险增加相关，可能是远处转移的预测指标。本研究比较了有和无淋巴结（LN）转移的结直肠癌（CRC）患者中6种SDF1α单核苷酸多态性（SNP）的频率，并确定不同SDF-1α基因型的成纤维细胞是否影响癌细胞的增殖和迁移。

方法

本研究纳入了424例原发性T3期CRC患者，有或无淋巴结转移，中位随访时间为48个月。采用聚合酶链反应-序列特异性引物（PCR-SSP）技术鉴定多态性。从14例II期CRC患者中收集成纤维细胞，并评估成纤维细胞介导的癌细胞增殖和迁移增强情况。

结果

只有SDF1α-G801A多态性与LN转移相关。LN转移患者中GA/AA基因型的频率（54.8%）显著高于无LN转移患者（40.7%）。在后一组中，GA/AA基因型患者的无病生存期（74%）短于GG基因型患者（87.6%）。在有LN转移的患者中，无论基因型如何，无病生存期相似。GA/AA成纤维细胞中SDF-1α mRNA的表达是GG成纤维细胞中的三倍。GA/AA（而非GG）成纤维细胞增强了结肠癌细胞（HCT116）的增殖和迁移。这些作用被SDF-1α中和抗体阻断。