Table 1.
Overview of some key examples of serum glycoprotein biomarkers from recent literature for diseases that present with altered glycoprotein levels and glycosylation abnormalities
| Glycoprotein Biomarker | Disease | Detection on protein levels or altered glycoforms | Detection technique | Reference |
|---|---|---|---|---|
| Transferrina | – CDG | – Glycosylation abnormalities | – IEF, QTOF | [50] |
| – Sepsis | – Decrease in sialylation | – ELLA | [93] | |
| – Acute pancreatitis | – Increased fucosylation | – LC-MS/MS | [94] | |
| – Ovarian cancer | – Increase of concentration | – ELISA | [95]a | |
| α1-antitrypsin | – CDG | – Altered glycosylation | – 2DE | [36] |
| – Chronic obstructive pulmonary disease (COPD) | – Decreased concentration | – ELISA | [96] | |
| – Liver cirrhosis and liver cancer | – Core and outer arm fucosylation | – 2DE, MALDI-TOF – FLISA |
[97] | |
| – Lung cancer | – Altered glycosylation | – Lectin microarray, ELISA | [98] | |
| Haptoglobin | – CDG | – Altered glycosylation | – 2DE | [36] |
| – Long cancer | – sLeX increase | – HILIC, WAX-HPLC | [99] | |
| – Acute phase ovarian cancer | – sLeX increase | – 2DE, NP-HPLC | [100] | |
| – Stomach cancer | – sLeX increase | – 2DE, LC-MS/MS – ELISA – HILIC |
[101] | |
| – Pancreatic cancer | – Fucosylation | – MALDI-TOF – Immunoblot |
[102, 103] | |
| – Rheumatoid arthritis | – Reduced mannosylation | – 2DE, MALDI-TOF – WAX-HPLC – ELISA |
[104] | |
| – Pancreatic cancer | – Changes in sialylation | – LC-MS/MS | [94] | |
| – Gastric cancer | – Increase of concentration | – ELISA – MRM |
[105] | |
| Fetuin | – Hepatocellular carcinoma (HCC) | – Fucosylation | – LC-MS/MS – FLISA |
[106] |
| – Chronic pancreatitis, pancreatic cancer | – sLeX increase | – 2DE, WAX-HPLC, NP-HPLC, LC-MS/MS, MALDI-TOF | [107] | |
| α-1-acid glycoprotein | – CDG | – Altered glycosylation | – 2DE | [36] |
| – Acute phase ovarian cancer | – sLeX increase | – 2DE, NP-HPLC | [100] | |
| – Chronic pancreatitis, pancreatic cancer | – Increased branching and sLeX | – 2DE, WAX-HPLC, NP-HPLC, LC-MS/MS, MALDI-TOF | [107] | |
| – Rheumatoid arthritis | – Altered mannosylation | – 2DE, MALDI-TOF – WAX-HPLC – ELISA |
[104] | |
| Immunoglobulin G (IgG) | – Acute phase ovarian cancer | – sLeX increase | – 2DE, NP-HPLC | [100] |
| – Advanced ovarian cancer | – Reduced galactosylation and sialylation levels | – 2DE, NP-HPLC | [100] | |
| – Stomach cancer | – Core fucosylation | – 2DE, LC-MS/MS | [101] | |
| α1-antichymotrypsin | – Acute phase ovarian cancer | – sLeX increase | – 2DE, NP-HPLC | [100] |
| – Alzheimer’s disease | – Concentration | – Immunoassay | [108] | |
| α2-macroglobulin | – Sjögren’s syndrome | Abnormal glycosylation | Immunoblot | [109] |
| α-fetoproteina | – Liver diseases | – Core fucosylation, concentration | – 2DE, immunoblot | [110] |
| – Liver cancera | – Concentration | – Anti-body (liquid phase binding assay) | [67]a | |
| des-γ-carboxypro-thrombin | Liver diseases, liver cancer | Core fucosylation | – 2DE, immunoblot | [110] |
| Ferritin | Still’s disease, hemophagocytic syndrome | Altered glycosylation | Immunoassay | [111] |
| Ceruloplasmin | – CDG | – Low levels, glycosylation abnormalities | – 2DE | [50] |
| – Hepatocellular carcinoma (HCC) | – Upregulated, core fucosylation | – LC-MS/MS – 2DE, MALDI-TOF |
[112, 113] | |
| – Pancreatic cancer | – sLeX increase | – LC-MS/MS – Immunoblot |
[114] | |
| Thyroglobulina | – CDG | – Low levels, glycosylation abnormalities | – 2DE | [50] |
| – Thyroid cancer | – Increase of concentration | – Immunoassay | [115], [68]a | |
| Thyrotropin, Thyroid stimulating hormone | – CDG | – Low levels, altered glycosylation | – IEF, serum levels | [50, 116, 117] |
| – Thyroid function | – Increase of glycoprotein concentration | – Immunoassay | [118] | |
| Hemopexin | Hepatocellular carcinoma (HCC) | Fucosylation | – LC-MS/MS – FLISA |
[106] |
| Clusterin | – Stomach cancer | – Smaller N-glycans | – 2DE, LC-MS/MS | [101] |
| – Gastric cancer | – Decrease of concentration | – ELISA – MRM |
[105] | |
| – Clear cell renal cell carcinoma | – Decreased (core fucosylated) biantannary glycans | – SDS-PAGE, LC-MS/MS – Immunoblot |
[119] | |
| Leucine rich-α2-glycoprotein | Stomach cancer | Upregulation, altered glycosylation | 2DE, LC-MS/MS | [101, 120] |
| α-dystroglycan | Walker-Warburg syndrome | Hypoglycosylation | Immunoassay | [121] |
| Kininogen | – Colorectal cancer (CRC) | – Elevated sialylation and fucosylation | – LC-MS/MS – Lectin microarray |
[122] |
| – Colorectal cancer (CRC) | – Increase of concentration | – MALDI-TOF – ELISA – Immunostaining |
[123] | |
| Kallistatin | Liver cirrhosis | Increase of concentration | ELISA | [124] |
| Afamin | – Metabolic syndrome | – Increase of concentration | – ELISA | [125] |
| – Gastric cancer | – Decrease of concentration | – ELISA – MRM |
[105] | |
| Prostate Specific Antigen (PSA)a | Prostate cancer | Increase of concentration | Immunoassay | [126], [68]a |
| Human chorionic gonadotrophin (hCG) | – Ovarian tumors – Testicular tumors |
Increase of concentration | Immunoassay | [68], [66]a |
| Apolipoprotein (A-1)a | Ovarian cancer | Decrease of concentration | ELISA | [95]a |
| Transthyretin, prealbumina | Ovarian cancer | Decrease of concentration | ELISA | [95]a |
| β2-microglobulina | Ovarian cancer | Increase of concentration | ELISA | [95]a |
| Cancer antigen 125 (CA125) or MUC16a | Ovarian cancer | Increase of concentration | ELISA | [67, 95]a |
| Carbohydrate antigen 19–9 (CA19-9)a | – Pancreatic cancer Ovarian cancer | sLea on mucin glycoproteins | ELISA | [64, 68]a |
| Cancer antigen 15–3 (CA15-3)a | Breast cancer | Sialylated O-linked oligosaccharide on MUC1 | ELISA | [67, 68]a |
| CA27-29a (MUC1) | Breast cancer | Protein concentration | ELISA | [67, 68]a |
2DE 2D-electrophoresis; ELLA enzyme-linked lectin assay; FLISA Lectin-Fluorophore-linked Immunosorbent Assay; HILIC Hydrophilic Interaction Liquid Chromatography; sLe a Sialyl Lewis A structures; sLe X Sialyl Lewis X structures; WAX-HPLC weak anion exchange high performance liquid chromatography
aFDA approved