title: Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer.
abstract: Although doxorubicin (Doxo) and docetaxel (Docet) in combination are widely used in treatment regimens for a broad spectrum of breast cancer patients, a major obstacle has emerged in that some patients are intrinsically resistant to these chemotherapeutics. Our study aimed to discover potential prediction markers of drug resistance in needle-biopsied tissues of breast cancer patients prior to neoadjuvant chemotherapy. Tissues collected before chemotherapy were analyzed by mass spectrometry. A total of 2,331 proteins were identified and comparatively quantified between drug sensitive (DS) and drug resistant (DR) patient groups by spectral count. Of them, 298 proteins were differentially expressed by more than 1.5-fold. Some of the differentially expressed proteins (DEPs) were further confirmed by Western blotting. Bioinformatic analysis revealed that the DEPs were largely associated with drug metabolism, acute phase response signaling, and fatty acid elongation in mitochondria. Clinical validation of two selected proteins by immunohistochemistry found that FKBP4 and S100A9 might be putative prediction markers in discriminating the DR group from the DS group of breast cancer patients. The results demonstrate that a quantitative proteomics/bioinformatics approach is useful for discovering prediction markers of drug resistance, and possibly for the development of a new therapeutic strategy.
authors.affiliation: BRI, Korea Institute of Science and Technology , 39-1 Hawolgok, Seongbuk, Seoul 136-791, Republic of Korea.
authors.forename: Won Suk
authors.initials: WS
authors.lastname: Yang
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.forename: Hee Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
authors.forename: Myeong-Hee
authors.initials: MH
authors.lastname: Yu
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Cheolju
authors.initials: C
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D040502:Calgranulin B / Q000032:analysis* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D016000:Cluster Analysis; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D020360:Neoadjuvant Therapy; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric; D022021:Tacrolimus Binding Proteins / Q000032:analysis* / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D040502:Calgranulin B; D020543:Proteome; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4