title: A serum protein profile predictive of the resistance to neoadjuvant chemotherapy in advanced breast cancers.
abstract: Prediction of the responses to neoadjuvant chemotherapy (NACT) can improve the treatment of patients with advanced breast cancer. Genes and proteins predictive of chemoresistance have been extensively studied in breast cancer tissues. However, noninvasive serum biomarkers capable of such prediction have been rarely exploited. Here, we performed profiling of N-glycosylated proteins in serum from fifteen advanced breast cancer patients (ten patients sensitive to and five patients resistant to NACT) to discover serum biomarkers of chemoresistance using a label-free liquid chromatography-tandem MS method. By performing a series of statistical analyses of the proteomic data, we selected thirteen biomarker candidates and tested their differential serum levels by Western blotting in 13 independent samples (eight patients sensitive to and five patients resistant to NACT). Among the candidates, we then selected the final set of six potential serum biomarkers (AHSG, APOB, C3, C9, CP, and ORM1) whose differential expression was confirmed in the independent samples. Finally, we demonstrated that a multivariate classification model using the six proteins could predict responses to NACT and further predict relapse-free survival of patients. In summary, global N-glycoproteome profile in serum revealed a protein pattern predictive of the responses to NACT, which can be further validated in large clinical studies.
authors.affiliation: Department of Chemistry, Korea University, Seoul, Republic of Korea.
authors.forename: Seok-Won
authors.initials: SW
authors.lastname: Hyung
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Jong-Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Byunghee
authors.initials: B
authors.lastname: Shin
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Jung
authors.forename: Jong-Moon
authors.initials: JM
authors.lastname: Park
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Sang-Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Myeong-Hee
authors.initials: MH
authors.lastname: Yu
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006023:Glycoproteins / Q000032:analysis* / Q000097:blood; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D040901:Proteomics; D013194:Staining and Labeling
chemical_list: D054316:Biomarkers, Pharmacological; D001798:Blood Proteins; D006023:Glycoproteins