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.

Autor: Lee CS; Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Taib NA; Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Ashrafzadeh A; Medical Biotechnology Laboratory, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Fadzli F; Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Harun F; Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Rahmat K; Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Hoong SM; Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Abdul-Rahman PS; 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., Hashim OH; 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.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2016 Feb 18; Vol. 11 (2), pp. e0149551. Date of Electronic Publication: 2016 Feb 18 (Print Publication: 2016).
DOI: 10.1371/journal.pone.0149551
Abstrakt: 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.
Databáze: MEDLINE
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