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
| Autor: | Penelope McManus, Tapan Mahapatra, Dalia ELFadl, Philip J. Drew, Vijay Agarwal, P.J. Kneeshaw, Victoria C. Hodgkinson, John N. Fox, Michael J. Lind, Lynn Cawkwell |
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| Rok vydání: | 2012 |
| Předmět: |
Gene isoform
medicine.medical_treatment Biophysics Estrogen receptor Breast Neoplasms Pilot Projects Drug resistance Proteomics Bioinformatics Biochemistry Breast cancer Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor medicine Humans Electrophoresis Gel Two-Dimensional Receptor Neoadjuvant therapy Chemotherapy business.industry medicine.disease Neoadjuvant Therapy 14-3-3 Proteins Receptors Estrogen Drug Resistance Neoplasm Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Cancer research Feasibility Studies Female business |
| Zdroj: | Journal of Proteomics. 75:2745-2752 |
| ISSN: | 1874-3919 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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