Label-Free Proteomic Analysis of Breast Cancer Molecular Subtypes

To better characterize the cellular
pathways involved in breast
cancer molecular subtypes, we performed a proteomic study using a
label-free LC–MS strategy for determining the proteomic profile
of Luminal A, Luminal-HER2, HER2-positive, and triple-negative (TN)
breast tumors compared with healthy mammary tissue. This comparison
aimed to identify the aberrant processes specific for each subtype
and might help to refine our understanding regarding breast cancer
biology. Our results address important molecular features (both specific
and commonly shared) that explain the biological behavior of each
subtype. Changes in proteins related to cytoskeletal organization
were found in all tumor subtypes, indicating that breast tumors are
under constant structural modifications to invade and metastasize.
We also found changes in cell-adhesion processes in all molecular
subtypes, corroborating that invasiveness is a common property of
breast cancer cells. Luminal-HER2 and HER2 tumors also presented altered
cell cycle regulation, as shown by the several DNA repair-related
proteins. An altered immune response was also found as a common process
in the Luminal A, Luminal-HER2, and TN subtypes, and complement was
the most important pathway. Analysis of the TN subtype revealed blood
coagulation as the most relevant biological process.

为更好地表征与乳腺癌分子亚型相关的细胞通路，我们采用无标记液相色谱-质谱（label-free LC–MS）技术开展蛋白质组学研究，对比分析腔A型（Luminal A）、腔型-HER2型（Luminal-HER2）、HER2阳性型及三阴性（TN）乳腺肿瘤与健康乳腺组织的蛋白质组特征。本对比研究旨在识别各亚型特有的异常生物学过程，有助于深化我们对乳腺癌生物学的认知。本研究结果揭示了各亚型兼具特异性与共通性的关键分子特征，可解释不同亚型的生物学行为。研究发现，所有肿瘤亚型均存在与细胞骨架组织相关的蛋白质表达变化，表明乳腺肿瘤始终处于结构性重塑过程中，以实现侵袭与转移。所有分子亚型的细胞黏附过程均发生改变，进一步证实侵袭性是乳腺癌细胞的共同特性。腔型-HER2型与HER2阳性型肿瘤还存在细胞周期调控异常，表现为多个DNA修复相关蛋白的表达改变。腔A型、腔型-HER2型及三阴性亚型还存在免疫应答异常，其中补体系统是最为关键的通路。针对三阴性亚型的分析显示，血液凝固是其最相关的生物学过程。