Distinct gene expression profiles between primary breast cancers and brain metastases from pair-matched samples
Distinct gene expression profiles between primary breast cancers and brain metastases from pair-matched samples
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DOI：
10.1038/s41598-019-50099-y
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发表时间：
2019-09-16
影响因子：
4.6
通讯作者：
Iwata, Hiroji
中科院分区：
文献类型：
--
作者：
Iwamoto, Takayuki;Niikura, Naoki;Iwata, Hiroji
我们的目标是确定乳腺癌的临床病理标志物和免疫相关基因特征在脑转移中是否表现出任何变化，以及先前报道的与脑转移和上皮-间充质转化(EMT)显著相关的基因在我们的数据集中是否可重复性和一致性。来自日本临床肿瘤组乳腺癌研究组的16个配对样本来自诊断为乳腺癌和脑转移的原发乳腺癌。比较了免疫相关基因、脑转移相关基因和EMT相关基因在原发乳腺癌和脑转移癌中的表达谱。对41种FDA批准的或正在研究中的脑转移药物的潜在治疗靶基因进行了探索。免疫相关信号在脑转移癌中的基因表达显著低于在原发乳腺癌中的表达。与脑转移和EMT相关的大多数基因在两组中均未检测到显著差异。在41个候选治疗靶点中，VEGFA和DNMT3A在脑转移瘤中的基因表达显著升高。我们发现，在原发乳腺癌和脑转移癌之间存在不同的基因表达模式。需要进一步的研究来探索这些不同的表达谱是否源于疾病状态或构成疾病状态的基础，并比较脑转移瘤和其他部位之间的这些特征。
Our objectives were to determine whether clinic-pathological markers and immune-related gene signatures in breast cancer exhibit any change upon brain metastasis and whether previously reported genes significantly associated with brain metastases and the epithelial-mesenchymal transition (EMT) were reproducible and consistent in our dataset. Sixteen pair-matched samples from primary breast cancers and brain metastases diagnosed were collected from the Japan Clinical Oncology Group Breast Cancer Study Group. Gene expression profiles for immune-, brain metastases-, and EMT-related genes were compared between primary breast cancers and brain metastases. Potential therapeutic target genes of 41 FDA-approved or under-investigation agents for brain metastases were explored. Immunerelated signatures exhibited significantly lower gene expression in brain metastases than in primary breast cancers. No significant differences were detected for the majority of genes associated with brain metastases and EMT in the two groups. Among 41 therapeutic target candidates, VEGFA and DNMT3A demonstrated significantly higher gene expression in brain metastases. We found that distinct patterns of gene expression exist between primary breast cancers and brain metastases. Further studies are needed to explore whether these distinct expression profiles derive from or underlie disease status and compare these features between metastases to the brain and other sites.