Urokinase receptor splice variant uPAR-del4/5-associated gene expression in breast cancer: identification of rab31 as an independent prognostic factor
Urokinase receptor splice variant uPAR-del4/5-associated gene expression in breast cancer: identification of rab31 as an independent prognostic factor
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DOI：
10.1007/s10549-007-9782-6
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发表时间：
2008-09-01
影响因子：
3.8
通讯作者：
Foekens, John A.
中科院分区：
文献类型：
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作者：
Kotzsch, Matthias;Sieuwerts, Anieta M.;Foekens, John A.
目的评估uPA受体剪接变异体uPAR-del 4/5对淋巴结阴性乳腺癌患者的纯预后影响，并确定与高或低uPAR-del 4/5 mRNA水平相关的差异表达基因。终点为无远处转移生存期（DMFS）和总生存期（OS）。结果在多因素分析中，uPAR-del 4/5对DMFS（HR = 3.29，P < 0.001）和OS（HR = 2.87，P = 0.002）的传统预后因素的基础模型有显著贡献。使用微阵列，发现七个基因在具有高uPAR-del 4/5 mRNA表达的肿瘤样品和癌细胞系中上调。选择编码Ras癌基因家族成员rab 31的基因对280例患者的mRNA表达进行定量分析。在多变量分析中，高rab 31值与患者DMFS（HR = 2.27，P < 0.001）和OS（HR = 2.01，P = 0.008）的不良结局显着相关，独立于uPAR-del 4/5。uPAR-del 4/5和rab 31水平高的患者亚组显示出最差的DFS和OS（P < 0.001，两者）与两个factor.Conclusions值低的肿瘤相比，我们的研究结果表明，uPAR-del 4/5和rab 31 mRNA代表独立的乳腺癌预后标志物，可能是不同的，但可能相关的，肿瘤相关的信号通路的组成部分。
Purpose To evaluate the pure prognostic impact of the uPA-receptor splice variant uPAR-del4/5 for lymph node-negative breast cancer patients, and to identify differentially expressed genes associated with high or low uPAR-del4/5 mRNA levels.Patients and methods mRNA transcript levels were measured by real-time PCR in tumor samples from 280 node-negative breast cancer patients who had not received adjuvant systemic therapy. Endpoints were distant metastasis-free survival (DMFS) and overall survival (OS). Gene expression analysis was performed with RNA isolated from breast cancer tissue and breast cancer cell lines using Affymetrix U133a GeneChips.Results In multivariate analysis, uPAR-del4/5 significantly contributed to the base model of traditional prognostic factors for DMFS (HR = 3.29, P < 0.001) and OS (HR = 2.87, P = 0.002). Using microarrays, seven genes were found to be up-regulated in tumor samples and cancer cell lines with high uPAR-del4/5 mRNA expression. The gene encoding rab31, a member of the Ras oncogene family, was selected for quantitative analysis of mRNA expression in the set of 280 patients. High rab31 values were significantly associated with worse outcome of patients for DMFS (HR = 2.27, P < 0.001) and OS (HR = 2.01, P = 0.008) in multivariate analysis, independent from uPAR-del4/5. The patient subgroup with high uPAR-del4/5 and rab31 levels showed the worst DMFS and OS (P < 0.001, both) compared with tumors with low values of both factors.Conclusions Our results suggest that uPAR-del4/5 and rab31 mRNA represent independent prognostic markers in breast cancer and may be components of different, but possibly associated, tumor-relevant signaling pathways.