title: Serum immunoglobulin G Fc region N-glycosylation profiling by matrix-assisted laser desorption/ionization mass spectrometry can distinguish breast cancer patients from cancer-free controls.
abstract: Herein, we report that breast cancer (BC) patients can be distinguished from cancer-free (NC) controls by serum immunoglobulin G (IgG) crystallizable fragment (Fc) region N-glycosylation profiling using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Recently, there has been much progress in the field of tumor immunology. However, to date, the role and biomarker potential of IgG Fc region N-glycosylation, which affects the function of antibodies, have not been examined in BC. In the present study, we profiled serum IgG Fc region N-glycans in BC patients (N = 90) and NC controls (N = 54) using MALDI-MS. An IgG Fc region N-glycan-based multiple logistic regression model was produced which could distinguish BC patients from NC controls (area under the receiver operative characteristic curve = 0.874). Furthermore, stage 0 patients could also be distinguished using this model. These results suggest that an unknown humoral factor or soluble mediator affects IgGs from the earliest stage of breast cancer, and also suggests that IgG Fc region N-glycosylation may play a role in tumor biology. Although further investigation is required, our findings are the evidence that IgG N-glycan profiling has the potential to be used as a breast cancer biomarker and may provide the insights into tumor immunology.
authors.affiliation: Department of Breast Surgery, Kyoto University Hospital, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: nobuko75@kuhp.kyoto-u.ac.jp.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Kawaguchi-Sakita
authors.affiliation: Shimadzu Corporation, 1 Nishinokyo-Kuwabaracho, Nakagyo-ku, Kyoto 604-8511, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kaneshiro-Nakagawa
authors.affiliation: Department of Breast Surgery, Kyoto University Hospital, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawashima
authors.affiliation: Institute for Advanced Bioscience, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata 997-0052, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Department of Breast Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Tokiwa
authors.affiliation: Department of Breast Surgery, Kyoto University Hospital, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Shimadzu Corporation, 1 Nishinokyo-Kuwabaracho, Nakagyo-ku, Kyoto 604-8511, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kajihara
authors.affiliation: Shimadzu Corporation, 1 Nishinokyo-Kuwabaracho, Nakagyo-ku, Kyoto 604-8511, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Shimadzu Corporation, 1 Nishinokyo-Kuwabaracho, Nakagyo-ku, Kyoto 604-8511, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Iwamoto
authors.affiliation: Shimadzu Corporation, 1 Nishinokyo-Kuwabaracho, Nakagyo-ku, Kyoto 604-8511, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Breast Surgery, Kyoto University Hospital, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan; Department of Breast Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood*; D011134:Polysaccharides / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011134:Polysaccharides
keywords: Biomarker; Breast cancer; IgG Fc region N-glycosylation; Tumor immunity