Table 2.
Putative biomarkers for human cancers discovered by serum proteome analysis
| Cancer type | Candidate marker | Proteomics platform | Reference |
|---|---|---|---|
| Lung | Protein gene product 9.5 (tumor antigen) | 2-DE/MS | [146] |
| Alpha-HG, hepatocyte growth factor | MALDI-TOF-MS/ELISA | [147] | |
| 11 493, 6429, 8245, 5335, and 2538 Da | SELDI-TOF-MS | [148] | |
| Ig lambda chain, TTR, HG-alpha 2, two isoforms of serum amyloid protein, apolipoprotein A-I fragment | 2-DE/MALDI-TOF-MS | [149] | |
| CRP, SAA, mucin 1, and AIAT | Antibody array | [119] | |
| Phosphoglycerate kinase 1 (prediction outcome) | 2-DE/MS, ELISA, expression microarray, tissue microarray | [150] | |
| SAA | MALDI-TOF-MS, ELISA | [151] | |
| Autoantibodies against annexins I and II, IL6 | 2-DE/Western blotting, MALDI-TOF-MS | [152] | |
| Liver | Pro-Apolipoprotein, A2HSG apolipoprotein A-IV, carboxy terminal fragment of albumin (down-regulated); leucine-rich alpha-2-glycoprotein, A1AT, A2MG, HG Hp2, HG precursor, serum paraoxonase, complement C3 and complement C4A (up-regulated) | 2-DE/MALDI-TOF-TOF | [153] |
| 5808, 8936, 9509, and 11 707 (m/z) | SELDI-TOF-MS | [154] | |
| GP73 | Lectin extraction, 2-DE/LC-MS/MS, Immunoblotting | [155] | |
| GP73 | Immunoblotting | [156] | |
| (19 proteins were found to be hyperfucosylated in cancer) Fc-Hemopexin, Fc-GP73d, Fc-HBsAge, Fc-AFP, Fc-A1AG, Fc-A1ACT, Fc-A1AT, Fc-Serotransferrin, Fc-Ceruloplasmin, Fc-A2MG, Fc-A2HSG, Fc-HG, Fc-Fibrinogen gamma chain precursor (P)4, Fc-Complement factor B, Fc-IgG, Fc-IgA, Fc-APO-D, Fc-Ig M, and Fc-Kininogen | Lectin extraction, 2-DE/LC-MS/MS, immunoblotting | [157] | |
| Carboxy terminal fragment of complement C3, apolipoprotein A1 isoform | 2-DE/MALDI-TOF-MS | [158] | |
| C-terminal part of the V10 fragment of vitronectin (8900 Da) | SELDI-TOF-MS | [159] | |
| – | SELDI-TOF-MS | [160] | |
| AFP glycoforms | IEF/ESI-MS | [161] | |
| AFP glycoforms | HPLC- MALDI-TOF-MS | [162] | |
| Breast | 4.3, 8.1, and 8.9 kDa | SELDI-TOF-MS | [87] |
| HSP27 (up-regulated), 14-3-3 sigma (down-regulated) | 2-DE/MALDI-TOF-MS | [163] | |
| HCRR oncoprotein | ELISA, MALDI-TOF-MS | [164] | |
| 4.3, 8.1, and 8.9 kDa, complement component C3a, C-terminal-truncated form of C3a | SELDI-TOF-MS | [165] | |
| 8138 and 5909 (m/z) | SELDI-TOF-MS | [166] | |
| – | SELDI-TOF-MS | [167] | |
| A1ACT, clusterin, complement factor B (up-regulated); A1AT (down-regulated) | 2-DE/MALDI-TOF-MS, ELISA | [168] | |
| Colon | HNP 1-3 | SELDI-TOF-MS | [169] |
| 17 247, 18 420, 5911, 9294, 4654, 21 694, 21 742, 5911, 8922, 8944, and 8817 (m/z) | SELDI-TOF-MS | [170] | |
| 5911, 8930, 8817, and 4476 (m/z) | SELDI-TOF-MS | [171] | |
| Nicotinamide N-methyltransferase | 2-DE/MALDI-TOF-MS | [172] | |
| Cancer-associated glycoform of HG | SDS-PAGE/blotting with biotinylated galectin-3 | [173] | |
| 2023.2, 3158.7, 3816.2, 4300.3, and 16 961.4 (m/z, up-regulated); 11 080.6 and 15 526.2 (m/z, down-regulated) | SELDI-TOF-MS | [174] | |
| Defensin alpha 6 | 2-DE, ELISA | [175] | |
| MMP9 | 1-DE, 2-DE, immunoblotting | [176] | |
| Prostate | Precursor forms of free PSA | Immunosorption, MALDI-TOF-MS, ESI-QTOF-MS | [177] |
| Prostate-specific membrane antigen | SELDI-TOF-MS, ProteinChip with immobilized anti-PSMA antibody | [178] | |
| 4475, 5074, 5382, 7024, 7820, 8141, 9149, 9507, and 9656 (m/z) | SELDI-TOF-MS | [85] | |
| – | SELDI-TOF-MS | [179] | |
| 2092, 2367, 2582, 3080, 4819, 5439, and 18 220 (m/z) | SELDI-TOF-MS | [86] | |
| NMP48 | SELDI-TOF-MS/MALDI-TOF/TOF-MS | [180] | |
| 16 087, 25 167, and 4283 (m/z) | SELDI-TOF-MS | [181] | |
| 15.2, 15.9, 17.5 kDa | SELDI-TOF-MS | [182] | |
| Serum von Willebrand factor, IgM, A1ACT, villin and IgG | Antibody array | [117] | |
| Autoantibodies signatures against 22 phage peptides | Phage protein array | [125] | |
| – | SELDI-TOF-MS | [183] | |
| – | QTOF-MS, weak cation exchange ProteinChip | [184] | |
| SAA | SELDI-TOF-MS, 2-DE, MS/MS | [185] | |
| Apolipoprotein A-II isoform (8946, m/z) | SELDI-TOF-MS, HPLC, GE, MS/MS | [186] | |
| Platelet factor 4 (7771, m/z) | C18 prefractionation, multidimensional LC, 2-DE, MALDI-TOF-MS, ELISA | [187] | |
| 3700, 3904, 3978, 4300, 5085, 5923, 6250, 6569, 6652, 7121, 7782, 7850, 7991, 9503, 15 265, 15 878, 16 003, and 16 068 | SELDI-TOF-MS | [188] | |
| 2.68 and 10.3 kDa (up-regulated); 17.9, 10.8, and 12.7 kDa (down-regulated) | SELDI-TOF-MS | [189] | |
| Free PSA, total PSA, low-molecular-weight free PSA elements | 2-DE | [190] | |
| free PSA, free PSA subforms, total PSA | Immunoadsorption, 2-DE | [191] | |
| Ovarian | 534, 989, 2111, 2251, and 2465 (m/z) | SELDI-TOF-MS | [83] |
| HG-alpha subunit | SELDI-TOF-MS, affinity chromatography, LC-MS/MS | [192] | |
| Neoplasia biomarkers: 4.1, 4.4, 7.7, 15.1, 15.9, 18.9, 23.0, 30.1, and 53.5 kDa (up-regulated), 12.9 kDa (down-regulated); Malignant neoplasia biomarkers: 3.1, 4.5, 5.1, 7.8, 8.2, 16.9, and 18.6 kDa (up-regulated), 13.9, 21.0, 28.0, 79.0, 93.0, and 106.7 kDa (down- regulated) | SELDI-TOF-MS | [84] | |
| Calgranulin A, B | 2-DE/LC-MS/MS | [193] | |
| HG-1 | LC-QTOF-MS, MALDI-TOF-MS | [194] | |
| Fibrinopeptide-A | Nano-LC-ESI-TOF-MS, FT-ICR MS | [195] | |
| SAA1 and its N-terminal arginine-truncated form | 2-DE, LC-MS/MS | [196] | |
| TTR, RBP, and CRP | ELISA, immunoprecipitation, MALDI-TOF-MS | [197] | |
| Intact and cleaved human Kallikrein11 | Immunoaffinity chromatography, RP-LC, N-terminal sequencing, ELISA | [198] | |
| Apolipoprotein A1, a truncated form of TTR (down-regulated), a cleavage fragment of inter-alpha-trypsin inhibitor heavy chain H4 (up-regulated) | SELDI-TOF-MS | [199] | |
| Leukemia | Rho-GDI2 autoantibodies | 2-DE/MALDI-TOF-MS/Western blotting/Immunoprecipitation | [200] |
| An 11.7 kDa fragment of alpha-trypsin inhibitor, two contiguous fragments (19.9 and 11.9 kDa) of HG-2 | SELDI, LC-MS/MS | [201] | |
| A2HSG, complement-associated protein SP-40, RBP4 gene product, lipoprotein C-III, an unknown protein (down-regulated); Ig heavy-chain variant, proteosome 26S ATPase subunit 1, and HG-1 (up-regulated) | 2-DE/LC-MS/MS/LC-QTOF-MS | [202] | |
| PARC/CCL18 (chemokine) | 2-DE/LC-MS | [203] | |
| Melanoma | – | MALDI-TOF-MS | [204] |
| – | SELDI-TOF-MS | [205] | |
| 7568, 7938, 11 397, 11 686, 11 975, 13 874, 14 620, 15 158, and 15 880 (m/z) | MALDI-TOF-MS | [206] | |
| DJ-1 oncoprotein | 2-DE/MS | [207] | |
| Head and neck | – | MALDI-TOF-MS | [208] |
| Metallopanstimulin-1 | SELDI-TOF-MS immunoassay | [209] | |
| Metallopanstimulin | Immunoprecipitation, Western blotting | [210] | |
| SAA, amyloid related serum protein, HG | 2-DE/MALDI-TOF-MS | [211] | |
| Two isoforms of SAA | SELDI-TOF-MS/QTOF-MS | [212] | |
| Loss of clusterin | 2-DE/MALDI-TOF-MS/RT-PCR/Western blotting | [213] | |
| Pancreatic | CRP, A1AT, SAA, IgA, protein-induced vitamin K antagonist-II (up-regulated); plasma gelsolin (down-regulated) | Antibody array | [118] |
| Apolipoprotein E, A1ACT, inter-alpha-trypsin inhibitor | DIGE/MALDI-TOF/TOF-MS | [214] | |
| SAA | SELDI-TOF-MS | [215] | |
| – | SELDI-TOF-MS | [216] | |
| Anti-DDX48 autoantibodies | 2-DE/LC-MS/MS | [217] | |
| SAA, A1AT, A1ACT, inter-alpha-trypsin inhibitor | SPE/MALDI-TOF-MS | [218] | |
| – | SELDI-TOF-MS | [219] | |
| 3885, 3967, and 8929 m/z | SELDI-TOF-MS | [220] | |
| Hepatocarcinoma-intestine-pancreas/pancreatitis-associated-protein I | SELDI-TOF-MS/ELISA | [221] | |
| Brain | Pattern based on 274 peptides | MALDI-TOF-MS, magnetic particle-based format | [59] |
| SAA | SELDI-TOF-MS | [222] | |
| Gastric | 3946, 3503, and 15 958 Da | SELDI-TOF-MS | [223] |
| Thrombin light chain A | SELDI-TOF-MS/MALDI-TOF-MS/QTOF-MS | [224] | |
| Cathepsin B (up-regulated) | 2-DE/Western blotting/immunohistochemistry | [225] | |
| HG, SAA | 2-DE/MS | [226] | |
| 7567, 15 117, 15 326, 15 847, 7934, 4524, 8052, 6982, and 4714 Da (up-regulated); 5252, 2675, 5546, 5340, 4177, 3 995, and 3245 Da (down-regulated) | SELDI-TOF-MS | [227] | |
| Renal | 3900, 4107, 4153, 5352, and 5987 Da | SELDI-TOF-MS | [228] |
| Serum amyloid alpha, and its des-Arginine and des-Arginine/des-Serine variants at the N-terminus | SELDI-TOF-MS | [229] | |
| SAA, CRP (up-regulated) (after four doses of IL-2) | SELDI immunoaffinity capture | [230] | |
| 4151 and 8968 (m/z) | SELDI-TOF-MS | [231] | |
| Multiple variants of serum amyloid alpha | SELDI-TOF-MS | [232] | |
| Testicle | Germ cell specific isoenzyme of alkaline phosphatase (GCAP) | 2-DE, ion-exchange chromatography, and Western blotting | [233] |