國家衛生研究院 NHRI:Item 3990099045/8878
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    題名: Analysis of differentially expressed novel post-translational modifications of plasma apolipoprotein E in Taiwanese females with breast cancer
    作者: Uen, YH;Liao, CC;Lin, JC;Pan, YH;Liu, YC;Chen, YC;Chen, WJ;Tai, CC;Lee, KW;Liu, YR;Lin, HT;Lin, CY
    貢獻者: National Institute of Cancer Research
    摘要: APOE epsilon2 or epsilon4 alleles being used as indicators of breast cancer risk is 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 ( upward arrow1.45-fold), E7 ( upward arrow1.45-fold), E11 ( upward arrow1.19-fold), E77 ( upward arrow2.02-fold), E87 ( upward arrow2.02-fold), and Q98 ( upward arrow1.62-fold) residues; dimethylation at the Q187 ( upward arrow1.44-fold) residue; dihydroxylation at the R92 ( upward arrow1.25-fold), K95 ( upward arrow1.25-fold), and R103 ( upward arrow1.25-fold) residues; and glycosylation at the S129 ( upward arrow1.14-fold) residue. The clustered methylation and dihydroxylation of plasma ApoE proteins may a play role in breast cancer. BIOLOGICAL SIGNIFICANCE: Our study describes a combinatorial approach of 1D SDS-PAGE, in-gel digestion, and nano-LC-MS that provides a label-free, comparative post-translation modification (PTM) quantification strategy to investigate apolipoprotein E (ApoE) in plasma from breast cancer patients versus normal volunteers and to inspect novel differentially expressed PTMs of ApoE associated with breast cancer risk. Four novel PTMs, i.e., methylation, dimethylation, dihydroxylation, and glycosylation, of ApoE were identified and included in a model of the molecular electrostatic potential. The clustered methylation and dihydroxylation of plasma ApoE proteins may a play role in breast cancer.
    日期: 2015-08
    關聯: Journal of Proteomics. 2015 Aug;126:252-262.
    Link to: http://dx.doi.org/10.1016/j.jprot.2015.05.038
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1874-3919&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000359884600023
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84938568492
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