CXCR4 是胃癌多西紫杉醇敏感性的一个潜在预测标志物。
CXCR4, a potential predictive marker for docetaxel sensitivity in gastric cancer.
机构信息
The Comprehensive Cancer Center, of Drum Tower Hospital, affiliated to the Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, PR China.
出版信息
Anticancer Res. 2010 Jun;30(6):2209-16.
UNLABELLED
The aim of this study was to explore predictive genes involved in docetaxel sensitivity of gastric cancer.
MATERIALS AND METHODS
Microarray analysis was performed to explore various gene expression levels between parental and docetaxel-resistant cells. A panel of 11 genes selected according to microarray analysis were validated and tested further in 11 cancer cell lines, resulting in 4 genes, CXCR4, CDK6, USP15 and CDH1. Histoculture drug response assay (HDRA) was used to examine docetaxel sensitivity, while qRT-PCR was used to measure the mRNA levels of the genes in 25 surgically dissected gastric cancer specimens.
RESULTS
Only CXCR4 mRNA levels in gastric cancer tissues were correlated with docetaxel sensitivity (R(2)=0.23, p=0.019) and significantly higher in resistant specimens (p=0.038). AMD3100, a CXCR4 antagonist, enhanced the docetaxel cytotoxicity in vitro.
CONCLUSION
CXCR4 mRNA expression levels may be a potential predictive biomarker in gastric cancer.
目的
本研究旨在探索与胃癌多西紫杉醇敏感性相关的预测基因。
材料与方法
采用基因芯片分析方法，探讨亲本细胞与多西紫杉醇耐药细胞之间的各种基因表达水平。根据基因芯片分析选择了一组 11 个基因进行验证，并在 11 种癌细胞系中进一步检测，得到 4 个基因，CXCR4、CDK6、USP15 和 CDH1。组织培养药物反应测定（HDRA）用于检测多西紫杉醇敏感性，而 qRT-PCR 用于测量 25 个手术切除的胃癌标本中基因的 mRNA 水平。
结果
仅胃癌组织中的 CXCR4 mRNA 水平与多西紫杉醇敏感性相关（R²=0.23，p=0.019），且耐药标本中显著升高（p=0.038）。AMD3100，一种 CXCR4 拮抗剂，增强了体外多西紫杉醇的细胞毒性。
结论
CXCR4 mRNA 表达水平可能是胃癌的潜在预测生物标志物。
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