基于乳腺原发癌基因表达谱的预后分子分型研究  

Prognostic molecular classification of breast cancers based on gene expression profiling

作　　者：冯玉梅[1] 李晓青[1] 孙保存[2] 曹旭晨[2] 顾林[2] 牛昀[2] 郝希山[2] 

机构地区：[1]天津医科大学附属肿瘤医院生物化学及分子生物学室,300060 [2]天津医科大学附属肿瘤医院乳腺癌防治教育部重点实验室,300060

出　　处：《中华肿瘤杂志》2006年第12期900-906,共7页Chinese Journal of Oncology

基　　金：天津市科技发展计划资助项目(013182311);国家高技术研究发展(863)计划资助项目(2002AA2Z2011)

摘　　要：目的比较乳腺原发癌随访3年有远处转移病例与无远处转移病例的原发癌基因表达谱差异,筛选转移预后预测标志基因群,并探讨其用于乳腺癌患者预后分子分型的临床意义。方法以随访3年5例有远处转移和5例无远处转移的乳腺癌患者作为分析病例,采用含21 329个人功能基因的Oligo芯片筛选预后不同的乳腺原发癌组织差异表达基因;基于差异表达基因分别对10例分析病例和另外20例验证病例进行k-mean聚类分析;利用逐一剔除法去除对聚类没有贡献的基因,得到可以预测乳腺癌患者转移和预后的标志基因群,用于乳腺癌患者预后的分子分型。结果利用10例不同预后的分析病例筛选得到的差异表达基因可以将30例乳腺癌患者分为预后良好和预后不良两个组;随访3年有远处转移的病例全部聚类在预后不良组,占该组的70．0％(7／10),而预后良好组中不含有远处转移的病例(0／20),两组3年内发生远处转移率的差异有统计学意义(P=0．03)。由104个基因组成的预后预测基因群中,5个与细胞黏附运动相关的基因在预后不良组较预后良好组均表达上调,2个与机体免疫应答相关的基因均下调,11个与细胞生长代谢相关的基因上调,14个与细胞生长代谢相关的基因下调,15个与细胞信号传导相关的基因表达量显著改变。结论通过乳腺癌有远处转移病例与无远处转移病例原发癌基因表达谱的比较研究,筛选得到可以预测乳腺癌患者转移和预后的基因群,且可反映高转移能力的乳腺原发癌中肿瘤细胞运动能力增强、机体免疫识别缺陷、细胞增殖活跃和信号传导异常的生物学特征,并能对乳腺癌患者进行预后分子分型,有望用于临床指导个体化治疗方案的选择。Objective To screen a set of gene markers related to metastasis and prognosis of breast cancer by comparison of gene expression profiles of primary breast cancers with distant metastasis to the cases without distant metastasis within 3 years follow-up, and to explore the clinical significance of those gene expression in prognostic molecular classification of breast cancer patients. Methods 5 cases with distant metastasis and 5 cases without distant metastasis within 3 years follow-up were used as training cases to compare their gene expression profiles by Oligo microarray hybridization containing 21 329 human functional genes. K-mean supervised cluster was done for 10 training cases and additional 20 testing cases based on the set of differential genes. ＂Leave-one-out＂ was used to eliminate useless genes to obtain optimal gene set that was used for prognostic molecular classification of breast cancer patients. Results The different genes screened out from gene expression profiling of primary breast cancers with and without distant metastasis could classify breast cancer patients into two sub-groups. All patients with distant metastasis were included in the ＂poor prognosis group＂ （7/10）, whereas there were no case showing distant metastasis in the ＂good prognosis group＂ （0/20）, with a statistically significant difference by exact probability test （P = 0.03）. In the set of 104 optimal genes, all 5 genes involved in cell adhesion and migration were up-regulated in cases with distant metastasis, all 2 genes related to immune response of host were down-regulated, 11 genes related to cell growth and metabolism were up-regulated and 14 down-regulated, and 15 genes related to cell signal transduetlon were significantly changed. Conclusion A set of genes involved in cell adhesion and migration, cell growth and metabolism, immune response mechanism, cell signal transduetion were screened out by comparing gene expression profiles of primary breast cancers with and without distant metastasis within 3

关 键 词：乳腺肿瘤 预后 分子分型 基因表达谱 

分 类 号：R737.9[医药卫生—肿瘤]