TY - JOUR
T1 - Functional proteomic profiling of triple-negative breast cancer
AU - Gromova, Irina
AU - Espinoza, Jaime A.
AU - Grauslund, Morten
AU - Santoni-Rugiu, Eric
AU - Talman, Maj Lis Møller
AU - van Oostrum, Jan
AU - Moreira, José M.A.
N1 - Funding Information:
Funding: This work was supported by a grant from the “A Race against Breast Cancer” foundation. The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data or in drafting this manuscript.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10
Y1 - 2021/10
N2 - Triple-negative breast cancer (TNBC) is a subtype of breast cancer that comprises various disease entities, all of which share a set of common features: a lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, respectively. Because of their receptor status, conventional chemotherapy remains the main therapeutic option for TNBC patients. We employed a reverse phase protein array approach (RPPA), complemented by immunohistochemistry, to quantitatively profile the activation state of 84 actionable key signaling intermediates and phosphoproteins in a set of 44 TNBC samples. We performed supervised and unsupervised approaches to proteomic data analysis to identify groups of samples sharing common characteristics that could be amenable to existing therapies. We found the heterogenous activation of multiple pathways, with PI3 K/AKT/mTOR signaling being the most common event. Some specific individualized therapeutic possibilities include the expression of oncogenic KIT in association with cytokeratin 15 and Erk1/2 positive tumors, both of which may have clinical value.
AB - Triple-negative breast cancer (TNBC) is a subtype of breast cancer that comprises various disease entities, all of which share a set of common features: a lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, respectively. Because of their receptor status, conventional chemotherapy remains the main therapeutic option for TNBC patients. We employed a reverse phase protein array approach (RPPA), complemented by immunohistochemistry, to quantitatively profile the activation state of 84 actionable key signaling intermediates and phosphoproteins in a set of 44 TNBC samples. We performed supervised and unsupervised approaches to proteomic data analysis to identify groups of samples sharing common characteristics that could be amenable to existing therapies. We found the heterogenous activation of multiple pathways, with PI3 K/AKT/mTOR signaling being the most common event. Some specific individualized therapeutic possibilities include the expression of oncogenic KIT in association with cytokeratin 15 and Erk1/2 positive tumors, both of which may have clinical value.
KW - Breast cancer
KW - Proteomics
KW - Reverse phase protein array
KW - Signaling pathway profiling
KW - Triple negative breast cancer
UR - http://www.scopus.com/inward/record.url?scp=85117067090&partnerID=8YFLogxK
U2 - 10.3390/cells10102768
DO - 10.3390/cells10102768
M3 - Article
C2 - 34685748
AN - SCOPUS:85117067090
SN - 2073-4409
VL - 10
JO - Cells
JF - Cells
IS - 10
M1 - 2768
ER -