title: Unmasking Heavily O-Glycosylated Serum Proteins Using Perchloric Acid: Identification of Serum Proteoglycan 4 and Protease C1 Inhibitor as Molecular Indicators for Screening of Breast Cancer.
abstract: Heavily glycosylated mucin glycopeptides such as CA 27.29 and CA 15-3 are currently being used as biomarkers for detection and monitoring of breast cancer. However, they are not well detected at the early stages of the cancer. In the present study, perchloric acid (PCA) was used to enhance detection of mucin-type O-glycosylated proteins in the serum in an attempt to identify new biomarkers for early stage breast cancer. Sensitivity and specificity of an earlier developed sandwich enzyme-linked lectin assay were significantly improved with the use of serum PCA isolates. When a pilot case-control study was performed using the serum PCA isolates of normal participants (n = 105) and patients with stage 0 (n = 31) and stage I (n = 48) breast cancer, higher levels of total O-glycosylated proteins in sera of both groups of early stage breast cancer patients compared to the normal control women were demonstrated. Further analysis by gel-based proteomics detected significant inverse altered abundance of proteoglycan 4 and plasma protease C1 inhibitor in both the early stages of breast cancer patients compared to the controls. Our data suggests that the ratio of serum proteoglycan 4 to protease C1 inhibitor may be used for screening of early breast cancer although this requires further validation in clinically representative populations.
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Cheng-Siang
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nur Aishah Mohd
authors.initials: NA
authors.lastname: Taib
authors.affiliation: Medical Biotechnology Laboratory, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ali
authors.initials: A
authors.lastname: Ashrafzadeh
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Farhana
authors.initials: F
authors.lastname: Fadzli
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Faizah
authors.initials: F
authors.lastname: Harun
authors.affiliation: Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kartini
authors.initials: K
authors.lastname: Rahmat
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: See Mee
authors.initials: SM
authors.lastname: Hoong
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|University of Malaya Centre for Proteomics Research, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Puteri Shafinaz
authors.initials: PS
authors.lastname: Abdul-Rahman
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|University of Malaya Centre for Proteomics Research, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Onn Haji
authors.initials: OH
authors.lastname: Hashim
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D050718:Complement C1 Inhibitor Protein; D055088:Early Detection of Cancer; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000378:metabolism; D009367:Neoplasm Staging; D010472:Perchlorates / Q000737:chemistry*; D011509:Proteoglycans / Q000097:blood*; D000093422:Glycated Serum Proteins; D000099158:Proteoglycan 4
chemical_list: D001798:Blood Proteins; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D006023:Glycoproteins; D037102:Lectins; D010472:Perchlorates; D011509:Proteoglycans; D000093422:Glycated Serum Proteins; C419197:PRG4 protein, human; D000099158:Proteoglycan 4; C469952:SERPING1 protein, human; C576518:Perchloric Acid