摘要
目的:通过乳腺原发癌与淋巴结转移癌基因表达谱的比较研究,筛选乳腺癌转移相关基因,探讨淋巴结转移阳性乳腺癌患者分子分型的临床意义。方法:采用cRNA扩增方法分别将乳腺原发癌和配对的淋巴结转移癌标记Cy3和Cy5的荧光探针,与点有21329个人功能基因的Oligo芯片进行配对杂交,筛选30例病例中至少16对样本(50%以上)有2.0倍以上相同差异表达趋势的基因;采用Cluster3.0对样本及病例进行非监督聚类分析。结果:共筛选得到95个差异表达基因,其中41个在转移癌中表达上调,54个下调;分别与细胞粘附和运动能力、细胞外基质、蛋白水解酶、信号传导与转录调节、细胞生长与凋亡相关。基于全基因表达谱对样本聚类将83.3%(25/30)病例的原发癌与其配对的淋巴结转移癌聚类在一起;基于差异表达基因对病例的聚类分析将30例患者分为2组,其中A组与B组比较,A组多为肿瘤体积T3～(4P<0.05)、ER阴性(P<0.05)、组织学Ⅲ级(P=0.073)和3年内发生远处转移(P=0.085)的预后较差的病例。结论:以同一病例乳腺原发癌与其淋巴结转移癌进行基因表达谱的比较分析,筛选得到的在多病例中有共同差异表达趋势的基因,涉及了与转移相关的重要生物学过程;同一病例的原发癌与转移癌聚类在一起,证实淋巴结转移癌是其原发癌高转移能力细胞的亚克隆,因而具有相近的基因表达谱,其中的差异基因即包含了涉及转移表型的基因改变,基于原发癌差异基因的表达谱可以将淋巴结转移阳性乳腺癌病例进行分子分组并能预测预后。
Objective：To sereen for and identify Meastais-related genes in breast cancer by conparing oncogern expresion maps of the primary breast cancer and matched lymph mode metastase,in onder to diseuss the clinical signifieance for moleeular grouping of the breast cancer patients with lymph node metastasis.Methods：cRNA amplification was used to labet primary tumor speeimens with Cy3 and lymph node metastases with Cy5.Paired samples were combined to hybridze to oligonueleotide microarrays with 21.329 functional human genes.The 2.0-fold or plus genes with the same differential-expression（up-regulated or down-regulated）potential were found in at least 16 of the 30 pairs of samples.Sixteen of the 30 sample pairs had genes differentially expressed at least 2.0-fold.Non-supervised cluster analysis（i.e hierarchical cluster analysis）was perfrmed for the specimens using Cluster3.0.Results：Atotal of 94 differentially expressed genes were identified,among which 41 showed upregulated expression and 53 showed downngulated expession in metasatic tissues,The genes were related to cell migration and adhesion, extracellular matrix , proteinase activity, signal transduction, transcription and regulation , as well as cell growth and apoptosis. Based on cluster analysis of the total gene expression maps, primary cancer in 83.3% （25/30） of the cases and the paired lymph node metastatic carcinomas grouped into clusters. The 30 cases were divided into 2 groups based on the cluster analysis of the differentially expressed genes, in which most of the cases in group A had poor prognosis with T3-4 tumors （P〈0.05）, were estrogen receptor negative （P〈0.05）, had histological grade- Ⅲ （P=0.073） and had distant metastasis （P=0.085）, compared to group B. Conclusions： The genes differentially expressed between primary breast cancer and lymph node metastasis hold the key to metastasis. Primary cancer and metastatic carcinoma are classified together in our cluster analysis, suggesting that lymph node metastatic c
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2006年第24期1393-1396,共4页
Chinese Journal of Clinical Oncology
基金
国家高技术研究发展计划(863)项目(编号:2002AA2Z2011)
天津市重大科技项关项目资助(编号:013182311)
关键词
乳腺癌
淋巴结转移
基因表达谱
聚类分析
Breast cancer
Lymph node metastasis
Microarray
Cluster-analysis
