Gene expression in histologically normal epithelium from breast cancer patients and from cancer-free prophylactic mastectomy patients shares a similar profile.

Gene expression in histologically normal epithelium from breast cancer patients and from cancer-free prophylactic mastectomy patients shares a similar profile.
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DOI:
10.1038/sj.bjc.6605576
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发表时间:
2010-04-13
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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我们假设在组织学正常(HN)上皮(NlEpi)中的基因表达在乳腺癌患者和接受乳房缩小整形术(RM)的一般风险对照者之间会存在差异,并且来自高危女性的无癌预防性乳房切除术(PM)样本的NlEpi中的基因表达会类似于HN基因表达。 我们分析了从冷冻组织中显微切割的73个NlEpi样本中的基因表达。在42个样本中,我们使用微阵列来比较18名RM患者、18名年龄匹配的HN(9名雌激素受体(ER)阳性,9名ER阴性)以及6名PM患者之间的基因表达。使用贝叶斯方法(BADGE)对数据进行分析,并在来自8名RM、17名HN和6名PM患者的31个独立NlEpi样本中用实时定量聚合酶链反应(qPCR)进行验证。 在RM和HN样本之间共有98个探针组(86个基因)存在差异表达。用这98个探针组进行层次分析,PM和HN样本聚在一起,远离RM样本。独立样本的qPCR验证在RM与HN患者相比准确率较高(84%)且一致,在RM与PM患者相比准确率较低(58%)且更具异质性。这86个基因涉及许多过程,包括转录和丝裂原活化蛋白激酶(MAPK)通路。 乳腺癌病例和对照者的NlEpi之间基因表达存在差异。在来自无癌乳房的高危NlEpi中可以辨别出癌症病例的基因表达谱。这表明该基因表达谱不是肿瘤的影响,而是可能标志着风险增加,并揭示了乳腺癌最早的基因组变化。
We hypothesised that gene expression in histologically normal (HN) epithelium (NlEpi) would differ between breast cancer patients and usual-risk controls undergoing reduction mammoplasty (RM), and that gene expression in NlEpi from cancer-free prophylactic mastectomy (PM) samples from high-risk women would resemble HN gene expression. We analysed gene expression in 73 NlEpi samples microdissected from frozen tissue. In 42 samples, we used microarrays to compare gene expression between 18 RM patients and 18 age-matched HN (9 oestrogen receptor (ER)+, 9 ER−) and 6 PM patients. Data were analysed using a Bayesian approach (BADGE), and validated with quantitative real-time PCR (qPCR) in 31 independent NlEpi samples from 8 RM, 17 HN, and 6 PM patients. A total of 98 probe sets (86 genes) were differentially expressed between RM and HN samples. Performing hierarchical analysis with these 98 probe sets, PM and HN samples clustered together, away from RM samples. qPCR validation of independent samples was high (84%) and uniform in RM compared with HN patients, and lower (58%), but more heterogeneous, in RM compared with PM patients. The 86 genes were implicated in many processes including transcription and the MAPK pathway. Gene expression differs between the NlEpi of breast cancer cases and controls. The profile of cancer cases can be discerned in high-risk NlEpi from cancer-free breasts. This suggests that the profile is not an effect of the tumour, but may mark increased risk and reveal the earliest genomic changes of breast cancer.
在412例患者的基于人群的队列中,乳腺癌的固有分子特征。
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