title: 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.
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.
authors.affiliation: Cancer Biology Proteomics Group, Postgraduate Medical Institute of the University of Hull, Hull, UK.
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Hodgkinson
authors.forename: Vijay
authors.initials: V
authors.lastname: Agarwal
authors.forename: Dalia
authors.initials: D
authors.lastname: ELFadl
authors.forename: John N
authors.initials: JN
authors.lastname: Fox
authors.forename: Penelope L
authors.initials: PL
authors.lastname: McManus
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Mahapatra
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kneeshaw
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Drew
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lind
authors.forename: Lynn
authors.initials: L
authors.lastname: Cawkwell
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D010865:Pilot Projects; D011960:Receptors, Estrogen / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen