title: Identification of predictive biomarkers for response to trastuzumab using plasma FUCA activity and N-glycan identified by MALDI-TOF-MS.
abstract: The aim of this study was to identify glycobiological biomarkers that indicate sensitivity to trastuzumab, a humanized monoclonal antibody against HER2 in plasma samples from breast cancer patients. Plasma samples were obtained from 24 breast cancer patients treated with trastuzumab monotherapy. The catalytic activities of plasma alpha1-6, fucosyltransferase (FUT8) and alpha-L fucosidase (FUCA) were analyzed using high-performance liquid chromatography (HPLC) and spectrophotometer, respectively. The plasma N-glycan profiles were investigated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Plasma FUT8 activity was not significantly correlated with either the clinical response or progression-free survival (PFS). On the other hand, plasma FUCA activity was significantly correlated with PFS (p < 0.05). The MALDI-TOF-MS analysis of the plasma N-glycan profile revealed that the expression of 2534 m/z N-glycan was lower in patients with progressive disease (PD) and was correlated with PFS. Low expression of 2534 m/z N-glycan discriminated between PD and non-PD with 75% sensitivity and 82% specificity. We demonstrated that the plasma FUCA activity and 2534 m/z N-glycan may be predictive biomarkers of sensitivity to trastuzumab. Our results suggest that glycosylation analysis may provide useful information for determining clinical cancer therapy and provide novel insight into biomarker studies using glycobiological tools in the field of breast cancer.
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Chikako
authors.initials: C
authors.lastname: Shimizu
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.forename: Masashi
authors.initials: M
authors.lastname: Andoh
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kohno
authors.forename: Kan
authors.initials: K
authors.lastname: Yonemori
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Koizumi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yokote
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D018572:Disease-Free Survival; D005260:Female; D005647:Fucosyltransferases / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry*; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D000068878:Trastuzumab; D016896:Treatment Outcome; D005644:alpha-L-Fucosidase / Q000097:blood* / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015415:Biomarkers; D005647:Fucosyltransferases; D011134:Polysaccharides; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D005644:alpha-L-Fucosidase