Aberrant glycosylation is a prominent feature of cancer, that can be used as targets to improve the existing cancer biomarkers, and help to assess metastasis risks, and therapeutic effects. We developed a targeted O-glycoproteomics method using serum specimens, and evaluated its utility in identifying advanced colorectal cancer (CRC) markers. To this end, we combined consecutive lectin affinity purification using Maclura pomifera lectin (MPL), jacalin, and Sambucus nigra lectin, which have affinities for the following O-glycans, that have received attention as cancer-related antigens, Tn (GalNAc-Ser/Thr), Sialyl Tn (Siaα2-6GalNAc-Ser/Thr), T (Galβ1-3GalNAc-Ser/Thr), Sialyl T (Siaα2-3Galβ1-GalNAc-Ser/Thr), and di-Sialyl T (Siaα2-3Galβ1-3[Siaα2-6] GalNAc-Ser/Thr), with a unique O-glycoproteomics approach. A total of 2,068 O-glycoforms derived from 265 proteins were identified in healthy individuals and patients with advanced CRC, of which 44 CRC-specific O-glycoforms were extracted. Particularly, five glycoproteins with T, Sialyl T, and di-Sialyl T antigens in specific peptide regions were evaluated quantitatively and statistically. We found that fibulin-2 (FBLN2) (aa330-349)/T antigen (area under the curve [AUC] = 0.92); macrophage colony-stimulating factor 1 (CSF1) (aa370-395)/(T + di-Sialyl T) (AUC = 0.94); macrophage mannose receptor 1 (MRC1) (aa1083-1101 and aa1215-1229)/T (AUC = 0.96 and 0.99); fibrinogen alpha chain (FGA) (aa354-367, aa511-527 and aa559-573)/Sialyl T (AUC = 0.98, 0.90 and 0.94); and complement component C7 (C7) (aa692-701)/di-Sialyl T (AUC = 1.00), can have high diagnostic efficacy to strategically predict advanced CRC groups. Hence, they could be promising markers for detection of advanced CRC, and provide new clinical test indicators along with lectins, such as MPL and jacalin. Our O-glycoproteomics platform provides a novel tool and resource, for researchers and clinicians seeking to better understand and treat advanced CRC.
Aberrant glycosylation of membrane proteins is a hallmark of cancer and a useful molecular marker for the diagnosis of breast cancer (BC). However, the molecular mechanisms by which altered glycosylation affects the malignant transformations associated with BC are poorly understood.Accordingly, we performed comparative membrane N-glycoproteomics using the human BC cell line pair, Hs578T, and its syngeneic normal cell line, Hs578Bst. A total of 359 N-glycoforms derived from 113 proteins were identified in both cell lines, of which 27 were found only in Hs578T cells.Significant changes in N-glycosylation were found in the lysosome-associated membrane protein 1 (LAMP1), the integrin family, and laminin. Confocal immunofluorescence microscopy images revealed the accumulation of lysosomes in the perinuclear space in cancer cells, which could be associated with marked changes in LAMP1 glycosylation, such as a decreased level of Site-specific glycosylation change in BC 2 Mass Spectrometry Advance Publication polylactosamine chains. Overall, the alterations in glycosylation may be involved in changes in the adhesion and degradation of BC cells.
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