Breast cancer is one of the most common malignancies among women
worldwide.The main limitations of the efficacy of currently used drugs for the
treatment of cancer include systemic toxicity, drug resistance and debilitating side
effects. Possible effective solutions to overcome these limitations are the use of
(i) overexpressed membrane proteins as targets to address the delivery system
of drugs encapsulated in second generation nanoparticles, and (ii) monoclonal
antibodies or aptamers against specific targets on the membrane of tumor cells.
In this context, this project outlines a strategy for the optimal selection of
membrane proteins in tumors focusing on the development of specific therapy
and diagnosis for breast cancer. Our strategy involves the use of the TCGA data
bank (The Cancer Genome Atlas) exploring transcriptome data from both tumor
and non-tumor breast human tissues; and other healthy tissues. By this strategy,
it was possible to identify membrane proteins with increased expression in tumor
tissue as compared to healthy tissue. A list of four target proteins (patent pending)
was proposed from this inference for 111 breast tumor patients that included the
different molecular subtypes; Luminal A, Luminal B, HER2 + and Triple Negative.
The validation process was performed using a cohort of 991 breast cancer
patients and 111 non-tumor samples; and patients were separated into clusters
according to their molecular subtype classification. The overexpression of these
four proteins was validated remaining high in all molecular subtypes.
Furthermore, immunofluorescence analysis also confirmed this data in breast
tumor cell lines from the different molecular subtypes, such as MDA-MB-231
(Triple Negative), T47D (Luminal A), HCC1954 (HER2+) in comparison with a
non-tumor breast line MCF10A. In addition, the identified proteins demonstrated
specificity and sensitivity, around 80%, according to data from the area under the
curve (AUC) of the ROC curve. To understand which intracellular pathways could
be involved with these proteins, analysis from the human interactome data was
performed. We observed that the proteins downstream the intracellular signaling
pathway present important roles in many processes of tumor progression.
Consequently, we expect that these proteins could be considered as suitable
targets for therapy with a lower rate of undesirable side effects and greater