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Differential expression of breast cancer-associated genes between stage- and age-matched tumor specimens from African- and Caucasian-American Women diagnosed with breast cancer

机译:来自被诊断患有乳腺癌的非裔和白人女性的阶段和年龄匹配的肿瘤标本中与乳腺癌相关的基因的差异表达

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Background Recent studies suggest that the poorer breast cancer outcome observed in African-American women (AAW) may, in part, result from underlying molecular factors. The purpose of this study was to investigate gene expression differences between Caucasian-American women (CAW) and AAW that may contribute to this poorer prognosis. Methods The expression of 84 genes involved in breast carcinoma prognosis, response to therapy, estrogen signaling, and tumor aggressiveness was assessed in age- and stage-matched CAW and AAW paraffin-embedded breast cancer specimens. The Wilcoxon–Mann–Whitney Test was used to identify genes with a significant difference in expression between CAW and AAW. To determine if the differentially expressed genes could segregate between the CAW and AAW, we performed semi-supervised principal component analysis (SSPCA). Results Twenty genes were differentially expressed between AAW and CAW. SSPCA incorporating these 20 genes segregated AAW and CAW into two distinct groups. AAW were significantly (p 1/S cell-cycle regulatory genes, decreased expression of cell-adhesion genes, and low to no expression of ESR1, PGR, ERBB2 and estrogen pathway targets. Conclusions The gene expression differences identified between AAW and CAW may contribute to more aggressive disease, resistance to therapy, enhanced metastatic potential and poor clinical outcome. These findings support the hypothesis that breast cancer specimens collected from AAW display distinct gene expression differences compared to similar tissues obtained from CAW. Additional population-based studies are necessary to determine if these gene expression variations contribute to the highly aggressive and treatment-resistant breast cancer phenotype frequently observed in AAW.
机译:背景技术最近的研究表明,在非洲裔美国妇女(AAW)中观察到的较差的乳腺癌结局可能部分是由潜在的分子因素引起的。这项研究的目的是调查高加索裔美国女性(CAW)和AAW之间的基因表达差异,这可能导致这种较差的预后。方法在年龄和阶段匹配的CAW和AAW石蜡包埋的乳腺癌标本中评估84个基因的表达与乳腺癌的预后,对治疗的反应,雌激素信号传导和肿瘤侵袭性有关。 Wilcoxon–Mann–Whitney检验用于鉴定在CAW和AAW之间表达差异显着的基因。为了确定差异表达的基因是否可以在CAW和AWW之间分离,我们进行了半监督主成分分析(SSPCA)。结果AAW和CAW之间有20个基因差异表达。整合了这20个基因的SSPCA将AWW和CAW分为两个不同的组。 AAW显着(p 1 / S细胞周期调控基因,细胞粘附基因表达降低,ESR1,PGR,ERBB2和雌激素途径靶点低表达或无表达。结论CAW可能导致更严重的疾病,对治疗的抵抗,转移潜力增强和临床结果差,这些发现支持以下假设:从AAW收集的乳腺癌标本与从CAW获得的相似组织相比具有明显的基因表达差异。研究是必要的,以确定这些基因表达的变化是否有助于AAW中经常观察到的高度侵袭性和抗治疗性的乳腺癌表型。

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