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Pilot and feasibility study: comparative proteomic analysis by 2-DE MALDI TOF/TOF MS reveals 14-3-3 proteins as putative biomarkers of response to neoadjuvant chemotherapy in ER-positive breast cancer

Lind, Michael J.; Agarwala, Vijay; Hodgkinson, Victoria C.; Agarwal, Vijay; ElFadl, Dalia; Fox, John N.; McManus, Penelope L.; Mahapatra, Tapan K.; Kneeshaw, Peter J.; Drew, Philip J.; Lind, Michael; Cawkwell, Lynn

Authors

Michael J. Lind

Vijay Agarwala

Victoria C. Hodgkinson

Vijay Agarwal

Dalia ElFadl

John N. Fox

Penelope L. McManus

Tapan K. Mahapatra

Peter J. Kneeshaw

Philip J. Drew

Professor Michael Lind M.J.Lind@hull.ac.uk
Foundation Professor of Oncology/ Head of the Joint Centre for Cancer Studies

Abstract

Neoadjuvant chemotherapy is used to treat oestrogen receptor-positive breast cancer however chemo-resistance is a major obstacle in this molecular subtype. The ability to predict tumour response would allow chemotherapy administration to be directed towards patients who would most benefit, thus maximising treatment efficacy. We aimed to identify protein biomarkers associated with response to neoadjuvant chemotherapy, in a pilot study using comparative 2-DE MALDI TOF/TOF MS proteomic analysis of breast tumour samples. A total of 3 comparative proteomic experiments were performed, comparing protein expression between chemotherapy-sensitive and chemotherapy-resistant oestrogen receptor-positive invasive ductal carcinoma tissue samples. This identified a list of 132 unique proteins that were significantly differentially expressed (≥ 2 fold) in chemotherapy resistant samples, 57 of which were identified in at least two experiments. Ingenuity® Pathway Analysis was used to map the 57 DEPs onto canonical signalling pathways. We implicate several isoforms of 14-3-3 family proteins (theta/tau, gamma, epsilon, beta/alpha and zeta/delta), which have previously been associated with chemotherapy resistance in breast cancer. Extensive clinical validation is now required to fully assess the role of these proteins as putative markers of chemotherapy response in luminal breast cancer subtypes.

Journal Article Type Article
Publication Date May 17, 2012
Journal Journal of proteomics
Print ISSN 1874-3919
Electronic ISSN 1876-7737
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 75
Issue 9
Pages 2745-2752
Institution Citation Hodgkinson, V. C., Agarwal, V., ElFadl, D., Fox, J. N., McManus, P. L., Mahapatra, T. K., …Cawkwell, L. (2012). Pilot and feasibility study: comparative proteomic analysis by 2-DE MALDI TOF/TOF MS reveals 14-3-3 proteins as putative biomarkers of response to neoadjuvant chemotherapy in ER-positive breast cancer. Journal of Proteomics, 75(9), (2745-2752). doi:10.1016/j.jprot.2012.03.049. ISSN 1874-3919
DOI https://doi.org/10.1016/j.jprot.2012.03.049
Keywords 14-3-3; Biomarkers; Breast cancer; Neoadjuvant chemotherapy; Mass spectrometry; Proteomics
Publisher URL https://www.sciencedirect.com/science/article/pii/S187439191200200X?via%3Dihub
PMID 22498883