Differentially expressed genes between primary cancer and paired lymph node metastases predict clinical outcome of node-positive breast cancer patients
Differentially expressed genes between primary cancer and paired lymph node metastases predict clinical outcome of node-positive breast cancer patients
复制标题
DOI：
10.1007/s10549-006-9385-7
复制
发表时间：
2007-07-01
影响因子：
3.8
通讯作者：
Hao, Xishan
中科院分区：
文献类型：
--
作者：
Feng, Yumei;Sun, Baocun;Hao, Xishan
腋窝淋巴结状态仍然是乳腺癌患者最有价值的预后因素。然而，大约20-30%的淋巴结阳性患者在15-30年内没有远处转移。重要的是开发能够预测远处转移风险的分子标记物，并开发患者定制的治疗策略。我们假设淋巴结转移可能代表了原发癌中转移性最强的部分。因此，我们试图通过微阵列来鉴定26例患者原发肿瘤及其配对淋巴结转移样本之间差异表达的基因。一组79个原发癌和转移样本之间的差异表达基因被鉴定，以正确区分大多数原发癌和淋巴结转移。30例淋巴结转移癌标本中基质金属蛋白酶2、纤维连接蛋白、成骨细胞特异性因子2、胶原蛋白XI α 1的表达均明显降低。这组基因还将35种原发性癌症分为两组，具有不同的预后：“高风险组”和“低风险组”。43个月内发生远处转移的危险度是“低危组”的4.65倍（95% CI 1.02-21.13，P = 0.047）。“这表明，由原发性癌症和淋巴结转移之间的79个差异表达基因组成的基因签名也可以预测淋巴结阳性患者的临床结果，并且基于基因签名的分子分类可以指导患者量身定制的治疗。
The axillary lymph node status remains the most valuable prognostic factor for breast cancer patients. However, approximately 20-30% of node-positive patients remain free of distant metastases within 15-30 years. It is important to develop molecular markers that are able to predict for the risk of distant metastasis and to develop patient-tailored therapy strategies. We hypothesize that the lymph node metastases may represent the most metastatic fraction of the primary cancers. Therefore, we sought to identify the differentially expressed genes by microarray between the primary tumors and their paired lymph node metastases samples collected from 26 patients. A set of 79 differentially expressed genes between primary cancers and metastasis samples was identified to correctly separate most of primary cancers from lymph node metastases. And decreased expression of matrix metalloproteinase 2, fibronectin, osteoblast specific factor 2, collagen type XI alpha 1 in lymph node metastases were further confirmed by real-time RT-PCR performed on 30 specimen pairs. This set of genes also classified 35 primary cancers into two groups with different prognosis: "high risk group" and "low risk group." Patients in "high risk group" had a 4.65-fold hazard ratio (95% CI 1.02-21.13, P = 0.047) to develop a distant metastasis within 43 months comparing with the "low risk group." This suggested that the gene signature consisting of 79 differentially expressed genes between primary cancers and lymph node metastases could also predict clinical outcome of node-positive patients, and that the molecular classification based on the gene signature could guide patient-tailored therapy.