Subtypes of breast cancer show preferential site of relapse
Subtypes of breast cancer show preferential site of relapse
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DOI：
10.1158/0008-5472.can-07-5644
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发表时间：
2008-05-01
期刊：
影响因子：
11.2
通讯作者：
Martens, John W. M.
中科院分区：
文献类型：
--
作者：
Smid, Marcel;Wang, Yixin;Martens, John W. M.
我们探讨了先前报道的五种乳腺癌分子亚型是否显示出对器官特异性复发的偏好，并寻找了相关的分子途径。描述亚型的“内在”基因列表被用于对344例淋巴结阴性患者的原发性乳腺肿瘤进行分类。Fisher精确检验用于确定仅接受局部治疗的患者中肿瘤亚型与远端复发的特定部位之间的关联。使用微阵列显著性分析和全局检验在各组中鉴定调节基因和途径。骨复发患者在管腔亚型中最丰富，但在基底亚型中发现少于预期。肺和脑复发患者的情况正好相反，说明肺复发的不存在是管腔A特异性的。最后，胸膜复发，虽然罕见，几乎完全在两个管腔亚型。许多差异表达的基因被确定，其中有几个是共同的亚型和该亚型的网站优先复发。WNT信号在基底亚型和脑特异性复发中上调，在管腔B亚型和骨特异性复发中下调。局灶性粘附在管腔A亚型中上调，但在肺复发中下调。乳腺癌中的五种主要分子亚型在转移到远处器官的能力方面明显不同，并且与其优选的远处转移部位共享生物学特征和途径。
We explored whether the five previously reported molecular subtypes in breast cancer show a preference for organ-specific relapse and searched for molecular pathways involved. The "intrinsic" gene list describing the subtypes was used to classify 344 primary breast tumors of lymph node-negative patients. Fisher exact tests were used to determine the association between a tumor subtype and a particular site of distant relapse in these patients who only received local treatment. Modulated genes and pathways were identified in the various groups using Significance Analysis of Microarrays and Global Testing. Bone relapse patients were most abundant in the luminal subtypes but were found less than expected in the basal subtype. The reverse was true for lung and brain relapse patients with the remark that absence of lung relapse,was luminal A specific. Finally, a pleura relapse, although rare, was found almost exclusively in both luminal subtypes. Many differentially expressed genes were identified, of which several were in common in a subtype and the site to which the subtype preferentially relapsed. WNT signaling was up-regulated in the basal subtype and in brain-specific relapse, and down-modulated in the luminal B subtype and in bone-specific relapse. Focal adhesion was found up-regulated in the luminal A subtype but down-regulated in lung relapse. The five major molecular subtypes in breast cancer are evidently different with regard to their ability to metastasize to distant organ(s), and share biological features and pathways with their preferred distant metastatic site.