A plasma protein derived TGFβ signature is a prognostic indicator in triple negative breast cancer
A plasma protein derived TGFβ signature is a prognostic indicator in triple negative breast cancer
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DOI：
10.1038/s41698-019-0082-5
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发表时间：
2019-04-02
影响因子：
7.9
通讯作者：
Hanash, Samir
中科院分区：
文献类型：
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作者：
Katayama, Hiroyuki;Tsou, Peiling;Hanash, Samir
我们研究了深入定量血浆蛋白质组分析的潜力，以揭示三阴性乳腺癌（TNBC）进展和转移的预测蛋白。对24名绝经前和24名绝经后新诊断的TNBC患者的样本进行了蛋白质组学分析，这些患者随后发生转移或未发生转移，结果发现43种与肿瘤进展相关的蛋白质。这些蛋白被发现与TGF β形成一个分层网络。通过整合小鼠TNBC模型的血浆蛋白数据，进一步证实和完善了这一特征，该模型包括具有快速和缓慢生长肿瘤的小鼠。在一个更大的验证队列中，由CLIC1、MAPRE1和SERPINA3组成的三个基因在完善的TGF β信号中显著地分层了总生存率（log-rank p = 0.0141），而与绝经状态、肿瘤分期、分级和大小无关。
We investigated the potential of in-depth quantitative plasma proteome analysis to uncover proteins predictive of progression and metastasis in triple negative breast cancer (TNBC). Analysis of samples from 24 pre-menopausal and 24 post-menopausal women with newly diagnosed TNBC who subsequently developed metastasis or remained metastasis free were utilized in the proteomic discovery set, which resulted in 43 proteins associated with tumor progression. These proteins were found to form a hierarchical network with TGF beta. The signature was further confirmed and refined by integrating plasma protein data from a murine TNBC model that encompassed mice with rapid- versus slow-growing tumors. Three genes consisting of CLIC1, MAPRE1, and SERPINA3 in the refined TGF beta signature significantly stratified overall survival (log-rank p = 0.0141) in a larger validation cohort irrespective of menopausal status, tumor stage, grade, and size.