Research Unit, Lucus Augusti University Hospital (HULA), Servizo Galego de Saúde (SERGAS), 27002 Lugo, Spain.
Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain.
Int J Mol Sci. 2020 Nov 10;21(22):8449. doi: 10.3390/ijms21228449.
Breast cancer (BC) is a molecularly heterogeneous disease that encompasses five major molecular subtypes (luminal A (LA), luminal B HER2 negative (LB-), luminal B HER2 positive (LB+), HER2 positive (HER2+) and triple negative breast cancer (TNBC)). BC treatment mainly depends on the identification of the specific subtype. Despite the correct identification, therapies could fail in some patients. Thus, further insights into the genetic and molecular status of the different BC subtypes could be very useful to improve the response of BC patients to the range of available therapies. In this way, we used gold nanoparticles (AuNPs, 12.96 ± 0.72 nm) as a scavenging tool in combination with Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) to quantitatively analyze the serum proteome alterations in the different breast cancer intrinsic subtypes. The differentially regulated proteins specific of each subtype were further analyzed with the bioinformatic tools STRING and PANTHER to identify the major molecular function, biological processes, cellular origin, protein class and biological pathways altered due to the heterogeneity in proteome of the different BC subtypes. Importantly, a profile of blood coagulation proteins was identified in the serum of HER2-overexpressing BC patients.
乳腺癌(BC)是一种分子异质性疾病,包含五个主要的分子亚型(管腔 A(LA)、管腔 B HER2 阴性(LB-)、管腔 B HER2 阳性(LB+)、HER2 阳性(HER2+)和三阴性乳腺癌(TNBC))。BC 的治疗主要取决于特定亚型的鉴定。尽管进行了正确的鉴定,一些患者的治疗仍可能失败。因此,进一步了解不同 BC 亚型的遗传和分子状态可能非常有助于提高 BC 患者对现有治疗方法的反应。为此,我们使用金纳米粒子(AuNPs,12.96±0.72nm)作为一种清除工具,结合序列窗口采集所有理论质量谱(SWATH-MS),定量分析不同乳腺癌内在亚型的血清蛋白质组变化。然后使用 STRING 和 PANTHER 等生物信息学工具进一步分析每个亚型特有的差异调节蛋白,以确定由于不同 BC 亚型蛋白质组的异质性而改变的主要分子功能、生物学过程、细胞起源、蛋白质类别和生物学途径。重要的是,在过表达 HER2 的 BC 患者的血清中鉴定出一组凝血蛋白。