title: Analysis of differentially expressed novel post-translational modifications of plasma apolipoprotein E in Taiwanese females with breast cancer.
abstract: APOE ε2 or ε4 alleles being used as indicators of breast cancer risk are controversial in Taiwanese females. We provide a concept for relative comparisons of post-translational modifications (PTMs) of plasma apolipoprotein E (ApoE) between normal controls and breast cancer patients to investigate the association of ApoE with breast cancer risk. APOE polymorphisms (ApoE isoforms) were not assessed in this study. The relative modification ratio (%) of 15 targeted and 21 modified peptides were evaluated by 1D SDS-PAGE, in-gel digestion, and label-free nano-LC/MS to compare normal controls with breast cancer patients. Plasma levels of the ApoE protein did not significantly differ between normal controls and breast cancer patients. Eleven sites with novel PTMs were identified from 7 pairs of differentially expressed targeted and modified peptides according to the relative modification ratio including methylation at the E3 (↑1.45-fold), E7 (↑1.45-fold), E11 (↑1.19-fold), E77 (↑2.02-fold), E87 (↑2.02-fold), and Q98 (↑1.62-fold) residues; dimethylation at the Q187 (↑1.44-fold) residue; dihydroxylation at the R92 (↑1.25-fold), K95 (↑1.25-fold), and R103 (↑1.25-fold) residues; and glycosylation at the S129 (↑1.14-fold) residue. The clustered methylation and dihydroxylation of plasma ApoE proteins may play a role in breast cancer.
authors.affiliation: Superintendent's Office, Chi-Mei Hospital Chiali, Tainan 722, Taiwan; Division of General Surgery, Department of Surgery, Chi-Mei Medical Center, Tainan 710, Taiwan; Department of Medical Research, Chi-Mei Medical Center, Tainan 710, Taiwan.
authors.forename: Yih-Huei
authors.initials: YH
authors.lastname: Uen
authors.affiliation: Proteomics Research Center, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Liao
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Jung-Chun
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Pan
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli County 35053, Taiwan.
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Liu
authors.affiliation: PhD, Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.
authors.forename: You-Chia
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan 26047, Taiwan.
authors.forename: Wei-Jung
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Taipei Medical University-Shuang-Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
authors.forename: Chih-Chun
authors.initials: CC
authors.lastname: Tai
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Kuan-Wei
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Yun-Ru
authors.initials: YR
authors.lastname: Liu
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Hung-Tse
authors.initials: HT
authors.lastname: Lin
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; PhD, Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan. Electronic address: cylin@tmu.edu.tw.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lin
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D020033:Protein Isoforms / Q000097:blood; D011499:Protein Processing, Post-Translational; D013624:Taiwan
chemical_list: D001057:Apolipoproteins E; D009363:Neoplasm Proteins; D020033:Protein Isoforms
keywords: Apolipoprotein E; Breast cancer; Extracted ion chromatogram; Label-free relative quantification; Plasma; Post-translational modification