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.