Characterization of a genomic signature of pregnancy identified in the breast.
Characterization of a genomic signature of pregnancy identified in the breast.
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DOI：
10.1158/1940-6207.capr-11-0021
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发表时间：
2011-09
期刊：
影响因子：
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通讯作者：
Arslan AA
中科院分区：
文献类型：
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作者：
Belitskaya-Lévy I;Zeleniuch-Jacquotte A;Russo J;Russo IH;Bordás P;Ahman J;Afanasyeva Y;Johansson R;Lenner P;Li X;de Cicco RL;Peri S;Ross E;Russo PA;Santucci-Pereira J;Sheriff FS;Slifker M;Hallmans G;Toniolo P;Arslan AA
本研究的目的是全面比较经产和未经产绝经后妇女乳腺的基因组图谱，以确定在妊娠后永久改变其表达的基因。该研究分为两个阶段。在发现阶段，我们比较了37例经产妇女和18例未经产绝经后妇女的乳腺基因组图谱。在验证阶段，在发现阶段观察到的基因组模式的确认，寻求在一个独立的一组30个经产和22个未经产的绝经后妇女。将RNA与含有针对54，675个转录物的探针的Affytelium HG_U133 Plus 2.0寡核苷酸阵列杂交;使用Affytelium GCOS软件扫描并分析图像。采用替代变量分析、逻辑回归分析和微阵列显著性分析来确定基因表达的统计学显著差异。错误发现率（FDR）方法用于控制多重比较。我们发现，208个基因（305个探针组）在研究的发现和验证阶段在经产和未经产妇女之间差异表达，FDR为10%，变化至少为1.25倍。这些基因参与转录调节、中心体组织、RNA剪接、细胞周期控制、粘附和分化。这些结果提供了有说服力的证据，证明足月妊娠会导致乳房的长期基因组变化。怀孕的基因组签名可以用作中间标记，以评估潜在的化学预防干预与激素模仿怀孕预防乳腺癌的影响。
The objective of the current study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts; scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression and significance analysis for microarrays were used to identify statistically significant differences in expression of genes. The False Discovery Rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at a FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell cycle control, adhesion and differentiation. The results provide persuasive evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer.