Browsing by Author "Liu, Ding"

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    Proteomics-Based Identification of Candidate Exosomal Glycoprotein Biomarkers and Their Value for Diagnosing Colorectal Cancer
    (Frontiers Media, 2021-10-19) Sun, Zujun; Ji, Shurong; Wu, Junlu; Tian, Jiale; Quan, Wenqiang; Shang, Anquan; Ji, Ping; Xiao, Weidong; Liu, Ding; Wang, Xuan; Li, Dong; Pediatrics, School of Medicine
    Early diagnosis and treatment of colorectal cancer (CRC) significantly improves the survival rate and quality of life. Here we screened for differences in glycoproteins associated with tumor-derived exosomes and validated their clinical value to serve as liquid biopsy biomarkers to diagnosed early CRC. Exosomes were extracted from paracancerous tissues, cancer tissues, and plasma. LC-MS/MS proteomic and glycoproteomics analyses were performed using an LTQ-Orbitrap Elite mass spectrometer. The differences in glycoproteins associated with exosomes of paracancerous tissues and cancer tissue were determined, and their levels in plasma exosomes were determined. Statistical analysis was performed to evaluate the diagnostic efficacy of exosome-associated glycoproteins for CRC. We found that the levels of fibrinogen beta chain (FGB) and beta-2-glycoprotein 1 (β2-GP1) in the exosome of CRC tissue were significantly higher compared with those of paracancerous tissues exosome. The areas under the receiver operating characteristic (ROC) curves of plasma exosomal FGB and β2-GP1 as biomarkers for CRC were 0.871 (95% CI = 0.786–0.914) and 0.834 (95% CI = 0.734–0.901), respectively, compared with those of the concentrations of carcinoembryonic antigen concentration [0.723 (95% CI = 0.679–0.853)] and carbohydrate antigen19-9 concentration [0.614 (95% CI = 0.543–0.715)]. Comprehensive proteomics analyses of plasma exosomal biomarkers in CRC identified biomarkers with significant diagnostic efficacy for early CRC, which can be measured using relatively non-invasive techniques.
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    Site-Specific N- and O-Glycosylation Analysis of Human Plasma Fibronectin
    (Frontiers Media, 2021-06-15) Liu, Ding; Wang, Shuaishuai; Zhang, Junping; Xiao, Weidong; Miao, Carol H.; Konkle, Barbara A.; Wan, Xiu-Feng; Li, Lei; Pediatrics, School of Medicine
    Human plasma fibronectin is an adhesive protein that plays a crucial role in wound healing. Many studies had indicated that glycans might mediate the expression and functions of fibronectin, yet a comprehensive understanding of its glycosylation is still missing. Here, we performed a comprehensive N- and O-glycosylation mapping of human plasma fibronectin and quantified the occurrence of each glycoform in a site-specific manner. Intact N-glycopeptides were enriched by zwitterionic hydrophilic interaction chromatography, and N-glycosite sites were localized by the 18O-labeling method. O-glycopeptide enrichment and O-glycosite identification were achieved by an enzyme-assisted site-specific extraction method. An RP–LC–MS/MS system functionalized with collision-induced dissociation and stepped normalized collision energy (sNCE)-HCD tandem mass was applied to analyze the glycoforms of fibronectin. A total of 6 N-glycosites and 53 O-glycosites were identified, which were occupied by 38 N-glycoforms and 16 O-glycoforms, respectively. Furthermore, 77.31% of N-glycans were sialylated, and O-glycosylation was dominated by the sialyl-T antigen. These site-specific glycosylation patterns on human fibronectin can facilitate functional analyses of fibronectin and therapeutics development.