Table 1.
A compilation of some of the most relevant studies that made use of samples from human cancer patients for the search of molecular biomarkers relevant to the diagnosis, prognosis, and/or therapeutical strategies in cancer research.
| Reference | Type of cancer | Methodology |
Sample | Patients |
Statistically validated targets |
Type of biomarker | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Prefractioning/enrichment | Target selection | Number of targets | Mass spectrometry (MS) approach | Controls | Cancer | Protein ID | Number of proteins | ||||
| (21) | Bladder | – | Isobaric tags for relative and absolute quantitation (iTRAQ) shotgun proteomics | 63 | Stable isotope dilution-selected reaction monitoring (SID-SRM) | Urine | 80 | 76 | Adiponectin, Afamin, apolipoprotein A-II precursor, CERU, complement C4 gamma chain; prothrombin | 6 | Diagnostic |
| (22) | Breast | Affinity depletion of 14 abundant proteins | Label-free (LF) shotgun proteomics | 34 | SID-SRM | Plasma | 4 | – | – | – | Diagnostic |
| (23) | Breast | SCX | iTRAQ shotgun proteomics | SID-SRM and LF-SRM | Tissue | 13 | 19 | Decorin; endoplasmin; 40S ribosomal; alpha actin; 14-3-3 zeta-delta | 49 | Prognostic | |
| (24) | Breast | Affinity depletion of abundant proteins | Transcriptomics; cell culture shotgun proteomics; bioinformatics | 107 | Labeled reference peptide (LRP)-SRM | Plasma | – | 76 | Fibronectin, clusterin, gelsolin and α-1-microglobulin/Inter-α-trypsin | Prognostic | |
| (25) | Breast | Immunoprecipitation | LF shotgun proteomics | 4 | SID-SRM | Serum; Tissue | 56 | 56 | PDCD4, CGN, G3BP2, OCIAD1 | 4 | Therapeutic |
| (26) | Breast | 2D-LC | Cell culture shotgun proteomics; literature | 319 | SID-SRM | Tissue | – | 244 | CLTC, DPYSL2; ABAT; many others | Diagnostic; prognostic | |
| (27) | Breast | Enrichment for membrane proteins | iTRAQ shotgun proteomics | 49 | SRM | Tissue | – | 27 | MFAP4; GP2 | 23 | Prognostic |
| (28) | Breast | SCX; Fe-IMAC | iTRAQ shotgun proteomics | 19 | SID-SRM | Tissue | – | 12 | PDS5; T1208; S352; S417; S13 | 15 | Prognostic |
| (29) | Breast | – | Transcriptomics database; LF shotgun proteomics; | 20 | SID-SRM | Tissue | – | 96 | KPNA2; CDK1 | 2 | Prognostic |
| (30) | Breast | – | LF shotgun proteomics | 3 | LF-SRM | Plasma | 204 | 216 | ApoA1; hemopexin; angiotensin; preprotein | 3 | Diagnostic |
| (31) | Breast | Off-gel IEF | iTRAQ shotgun proteomics; western blotting | 3 | SID-SRM | Tissue | 10 | 10 | Cofilin-1; p23 | 2 | Prognostic |
| (32) | Breast | – | Cell culture shotgun proteomics; literature | 1 | SID-SRM | Tissue | – | 40 | HER2 | Diagnostic; prognostic | |
| (33) | Breast | Precipitation and ultrafiltration | Literature | 5 | SID-SRM | Plasma | 20 | 20 | IGF1, IGF2, IBP2, IBP3, and A2GL | 5 | Diagnostic |
| (34) | Breast | – | LF shotgun proteomics | 100 | LF-pSRM | Tissue | – | 51 | ENPP1; UQCRFS1; GNB4 | – | Therapeutic |
| (35) | Breast | SPE | Literature | 6 | SID-SRM | Serum | 6 | 6 | Hyp3-bradykinin; Des-Arg9-bradykinin; Fib-α; C4a; ITIH4; Bradykinin | 6 | Diagnostic |
| (36) | Breast | Affinity depletion of abundant proteins; immunoaffinity enrichment | Literature | 1 | SID-SRM | Serum | 60 | 60 | sTfR-transferrin receptor | 1 | Therapeutic |
| (37) | Breast | Membrane protein extraction | Literature | 1 | SID-SRM | Tissue | – | 60 | P-gp | 1 | Prognostic |
| (38) | Colon | SDS-PAGE | Literature | 60 | 18O SID-SRM | Feces | 5 | 5 | L-plastin, filamin A, S100A9, hemoglobin, myeloperoxidase | 5 | Diagnostic |
| (15) | Colon | SDS-PAGE, RP, and SEC HPLC | LF shotgun proteomics | 40 | SID-SRM | Feces | 7 | 8 | a-1-antityrpsin, a-1-acid glycoprotein, complement C3, fibrinogen, haptoglobin, hemoglobin a, hemoglobin b, myeloblastin, transferrin | 9 | Diagnostic |
| (39) | Colon | Affinity depletion of 6 abundant proteins; SDS-PAGE | LF shotgun proteomics | 8 | LF-SRM | Plasma | 48 | 48 | CLU | 1 | Diagnostic |
| (40) | Colon | – | Literature | 7 | SID-SRM | Serum | 259 | 172 | ORM1, GSN, C9, HABP2 SAA2, C3 | 6 | Diagnostic |
| (41) | Colon | Ultracentrifugation and filtration to select NOP | LF shotgun peptidomics | 1 | SID-SRM | Urine | 25 | 24 | Collagen type 1 | 1 | Prognostic |
| (42) | Colon | Laser microdissection; SDS-PAGE | Literature | 22 | SID-SRM | Tissue | – | 3 | B-catenin; c-Src; c-Myc; PP2A | 4 | Prognostic |
| (43) | Colon | Cell membrane fractionation | iTRAQ shotgun proteomics | 105 | SID-SRM | Tissue | 16 | 33 | ITGA5, GPRC5A, PDGFRB, TFRC, Others (see Table 2) | 44 | Diagnostic; prognostic; therapeutic |
| (44) | Colon | – | Literature | 3 | Hyperplex-SRM | Tissue | – | 37 | AHCY, CTSD, LYZ | 3 | Prognostic |
| (45) | Endometrial | SCX | iTRAQ shotgun proteomics | 1 | mTRAQ-SRM | Tissue | 1 | 1 | PK | 1 | Diagnostic |
| (46) | Gastric | Laser microdissection | Literature | 1 | SID-SRM | Tissue | – | 130 | MET | 1 | Prognostic; therapeutic |
| (47) | Glioblastoma | – | Transcriptomics; shotgun proteomics; literature | 100 | SID-SRM | Tissue | – | – | Malectin; calnexin; LDHA; IDH; and many others | 32 | Therapeutic |
| (48) | Kidney | – | – | – | SWATH | Tissue | 9 | 9 | – | – | Diagnostic |
| (49) | Liver | Lectin enrichment for glycoproteins | Literature | 10 | SID-SRM | Plasma | 30 | 10 | AACT, A1AT, A1AG1, CERU | 4 | Diagnostic |
| (50) | Liver | Lectin enrichment for glycoproteins | Literature | 2 | SID-SRM | Plasma | 3 | 3 | A1AT; FETUA | Diagnostic | |
| (51) | Liver | – | cDNA microarray; copy number variation; somatic mutation; epigenetic; quantitative proteomics data | 50 | LRP-SRM | Serum | 36 | 36 | ANLN; FLNB; C4A; AFP | 4 | Diagnostic |
| (52) | Liver | Affinity depletion of 6 abundant proteins | Literature | 1 | SID-SRM | Serum | 95 | 60 | AFP | 1 | Diagnostic |
| (53) | Liver | mHFER enrichment for glycopeptides | shotgun proteomics | 49 | iCCM-SRM | Serum | 10 | 3 | 14 | ||
| (54) | Liver | Affinity depletion of 6 abundant proteins | LF shotgun proteomics | 4 | SID-SRM | Plasma | 10 | 1 | AGP; vitronectin; afamin precursor; Kininogen1 precursor | 4 | Diagnostic; prognostic; therapeutic |
| (55) | Liver | – | Literature | 2 | SID-SRM | Plasma | 40 | 41 | Vitronectin; AGP | 2 | Diagnostic |
| (56) | Liver | Aptamer-based fractionation | Gel-based proteomics | 1 | SID-SRM | Serum | 24 | 26 | ApoA1 | 1 | Diagnostic; prognostic |
| (57) | Liver | Aptamer-based proteominer depletion of abundant proteins | 2D-DIGE | 43 | SID-SRM | Serum | 6 | 6 | AFP, AFP-L3, DCP | – | Diagnostic |
| (58) | Liver | SDS-PAGE | LF shotgun proteomics | 31 | SID-SRM | Tissue | – | 50 | DDX39; FBLN5; MARCKS; SERPINH1; VCAN | 5 | Diagnostic |
| (59) | Liver | Hp affinity isolation | Literature | 1 | SID-SRM | Plasma | 20 | 10 | Haptoglobin-T3 | 1 | Prognostic |
| (60) | Liver | – | Literature | 2 | O18-SID-SRM | Serum | 10 | 10 | CLU-1; VIT-2 | 2 | Prognostic |
| (61) | Lung | Lectin fractionation | Literature | 2 | SID-SRM | Plasma | 33 | 33 | AGP, CP | 2 | Prognostic |
| (62) | Lung | Affinity depletion of 6 abundant proteins | LF shotgun proteomics | 34 | SID-SRM | Pleural effusion | 86 | 39 | ALCAM, CDH1, MUC1, SPINT1, THBS4 | 5 | Diagnostic |
| (63) | Lung | Enrichment for desthiobiotinylated and tyrosine-phosphorylated peptides | LF shotgun proteomics | 264 | LRP-SRM | Tissue | 5 | 5 | Kinases | Therapeutic | |
| (64) | Lung | Microdissection | Literature | 1 | SID-SRM | Tissue | – | 23 | EGFR | 1 | Therapeutic |
| (65) | Lung | Affinity depletion of albumin and IgG | Literature | 95 | SID-SRM | Plasma | 72 | 30 | ACTN1; ALDOA; ENO1; FLNA; G6PD; GPI; HSP90B1; ICAM1; ILK; LDHB; MSN; PGK1; PKM2; SPP1; TALDO1; THBS1; ZYX | 17 | Diagnostic |
| (66) | Lung | Affinity depletion of albumin and IgG | Literature | 371 | SID-SRM | Plasma | 123 | 124 | ISLR; BGH3; FIBA; TSP1; TETN; COIA1; LG3BP; LRP1; FRIL; PRDX1; GRP78; ALDOA; GSLG1 | 13 | Diagnostic |
| (67) | Lung | Immunoaffinity | Databases, literature | 5 | SID-SRM | Serum | 12 | 12 | TIMP1, SLPI, TFPI, TFPI2, and CEA | 5 | Diagnostic |
| (68) | Lung | Laser microdissection | LF shotgun proteomics | 6 | In sample internal standard-SRM | Tissue | – | 27 | Napsin-A, hAG-2 | 2 | Prognostic |
| (69) | Lung | – | LF shotgun proteomics | 705 | LF-SWATH | BALF | 12 | 12 | Haptoglobin, complement C4-A, glutathione S-transferase | 44 | Diagnostic |
| (70) | Lung | – | Literature | 1 | SID-SRM | Serum | 50 | 160 | Hp (subunits α and β) | 1 | Diagnostic |
| (71) | Lung | – | Literature | 2 | SID-SRM | Serum | 99 | 100 | SAA1 and SAA2 | 2 | Diagnostic |
| (72) | Lung | Immunoaffinity | Literature | 3 | SID-SRM | Serum | 4 | 6 | ProGRP isoform 1, ProGRP isoform 3, NSE | 3 | Diagnostic |
| (73) | Lung | SDS-PAGE | LF shotgun proteomics | 10 | SID, LRP, and LF-SRM | Tissue | – | – | β-galactosidase; alkaline phosphatase | 2 | Diagnostic |
| (74) | Melanoma | SDS-PAGE | Literature | 1 | SID-SRM | Tissue | – | 192 | BIM | 1 | Therapeutic |
| (75) | Melanoma | SDS-PAGE | Literature | 82 | SRM | Tissue | – | – | HSP70; VEGFR2; mTOR; IRS-4; GSK3; AKT1/2 | 6 | Therapeutic |
| (76) | Melanoma | – | Literature | 1 | SID-SRM | Tissue | 0 | 10 | SNCA | 1 | Prognostic |
| (77) | Mesothelial | Glycopeptides enrichment | MS-CSC; spectral libraries | 36 | LF-SRM | Serum | 26 | 49 | Intercellular adhesion molecule 1; basement membrane-specific heparan sulfate proteoglycan core protein; anthrax toxin receptor 1; serum paraoxonase/arylesterase 1; hypoxia upregulated protein 1; thrombospondin-1 | 6 | Diagnostic |
| (78) | Oral | – | Literature | 14 | LRP-SRM | Saliva | 8 | 22 | C1R; LCN2; SLPI; FAM49B; TAGLN2; CFB; C3; C4B; LRG1; SERPINA1 | 10 | Prognostic |
| (79) | Ovary | Combinatorial peptide libraries 2D-LC | LF shotgun proteomics | 134 | LF-SRM | Ascites fluid | – | 6 | AMBP, BCAM, BTD, CD109, CD14, COMP, CPN2, ECM1, FSTL1, HABP2, HSPG2, IGFBP3, KLK6, LBP, LGALS3BP, MIF, MSLN, MSN, MSRA5, PON1, PRG4, SERPINA10, SERPINC1, SERPIND1, SERPINF1, SHBG, TGFB1, THBS1, TIMP1, TNC | 30 | Diagnostic |
| (11) | Ovary | Affinity depletion of 12 abundant proteins; MudPIT; OFFGEL | LF shotgun proteomics | 51 | SID-SRM | Ascites fluid | 25 | 5 | GAPDH, MSLN, PKM1/2 | 3 | Diagnostic |
| (80) | Ovary | Affinity depletion of 14 abundant proteins | LF shotgun proteomics | 2 | SID-SRM | Tissue | 10 | 11 | WDR1 | 1 | Therapeutic |
| (81) | Ovary | Affinity depletion of 12 abundant proteins | Literature; computational prediction | 34 | SID-SRM | Plasma | 68 | 16 | AACT, APOA1, APOE, B2MG, C1R, CFAB, CO5, CO6, CO7, GELS, HPT, IC1, ITIH4, RET4, SHBG, TETN, THBG, TRFE, TTHY | 19 | Diagnostic |
| (82) | Ovary | Affinity depletion of 20 abundant proteins; SDS-PAGE | LF shotgun proteomics | 7 | LF-SRM | Plasma | 15 | 18 | 3 | Diagnostic | |
| (83) | Ovary | Affinity depletion of 20 abundant proteins; SDS-PAGE | LF shotgun proteomics | 2 | LF-SRM | Plasma | 1 | 3 | CLIC; TPM | 2 | Diagnostic |
| (84) | Pancreas | SDS-PAGE | Literature | 1 | SID-SRM | Cyst fluid | 5 | 10 | KRAS | 1 | Diagnostic |
| (85) | Pancreas | – | LF shotgun proteomics | 18 | LRP-SRM | Tissue | – | 9 | TGM2, PSAP, DPYSL3, SERPINF1, ARPC4, BRRP7, S100A11, CAN2, MVP, GC | 10 | Prognostic |
| (86) | Pancreas | 2D-nano-HPLC | iTRAQ shotgun proteomics | 1 | SRM | Tissue | 3 | 7 | Dihydropyrimidinase-like 3 | 1 | Therapeutic |
| (87) | Pancreas | Affinity depletion of six abundant proteins | Literature; database | 260 | SID-SRM | Plasma | 100 | 84 | KLKB1, IGFBP2, THBS1, PPBP, TXN, LDHB, IGFBP3, LRG1, C5, AGT, CPN2 | 11 | Diagnostic |
| (88) | Pancreas | Lectin affinity chromatography | TMT shotgun proteomics | 1 | SID-SRM | Serum | 115 | 26 | Serotransferrin | 1 | Diagnostic |
| (89) | Pancreas | Membrane and cytosolic fractions | Literature | 25 | SID-SRM | Tissue | – | 10 | dCK | 8 | Treatment |
| (90) | Pancreas | Affinity depletion of albumin and IgG | Shotgun proteomics (literature) | 5 | SID-SRM | Plasma | 40 | 20 | Gelsolin, lumican, TIMP1 | 3 | Diagnostic |
| (91) | Pancreas | Laser microdissection; immunohistochemistry | Shotgun proteomics | 170 | LRP-SRM | Tissue | 5 | 8 | ECH1, GLUT1 (GTR1), OLFM4, STML2 | 4 | Prognostic |
| (92) | Pancreas | Streptavidin affinity 2D-nano-HPLC | Shotgun proteomics | 4 | SRM | Tissue | 38 | 62 | FN1, PRELP, TGM2, AGRN | 4 | Diagnostic; therapeutic |
| (93) | Pancreas | Affinity depletion of high and medium abundant proteins | SILAC shotgun proteomics | 72 | SID-SRM | Serum | 20 | 20 | cystatin M, IGF binding protein 7, villin 2 | 3 | Diagnostic |
| (94) | Pancreas | – | Shotgun proteomics PTM (literature) | 1 | SID-SRM | Plasma | 21 | 70 | α-fibrinogen containing Hyp-530 and Hyp-565 | 1 | Diagnostic |
| (95) | Prostate | – | Databases, LF shotgun proteomics | 32 | LF-parallel reaction monitoring (PRM) | Urine | 15 | 15 | PROS1; HPR; PZP; SLAIN1 | 4 | Diagnostic |
| (96) | Prostate | SCX | Literature | 1 | SID-SRM | Serum | – | – | PSA | 1 | Diagnostic |
| (97) | Prostate | Depletion of 14 abundant proteins; immunoprecipitation | Literature | 2 | SID-SRM | Serum | – | – | proPSA; PSA | 2 | Diagnostic |
| (98) | Prostate | Glycopeptides enrichment | LF shotgun glycoproteomics | 39 | SID-SRM | Serum; Tissue | 66 | 77 | GALNTL4; FN; AZGP1; BGN; ECM1 | Diagnostic; Prognostic | |
| (99) | Prostate | Affinity depletion of abundant proteins; MCX | Literature | 1 | SID-SRM | Serum | 4 | 5 | PSA | Diagnostic | |
| (100) | Prostate | – | 2D-DIGE-MS | SID-SRM | Urine | 14 | 11 | Vinculin; PAP; galectin-3 | 3 | Diagnostic; prognostic | |
| (101) | Prostate | Microdissection; glycopeptides enrichment | LF shotgun glycoproteomics | 548 | SWATH | Tissue | 10 | 65 | N-acylethanolamine acid amidase; protein tyrosine kinase 7 | 3 | Diagnostic; prognostic |
| (102) | Prostate | High PH RP-HPLC | Literature | 1 | SID-SRM | Serum | 1 | 2 | PSA | 1 | Diagnostic |
| (103) | Prostate | Affinity depletion of 14 abundant proteins; high PH RP-HPLC | Literature | 2 | SID-SRM | Urine; serum | 23 | 14 | ARG2; PSA | 2 | Diagnostic |
| (104) | Prostate | Glycoprotein enrichment | Literature | 37 | SID-SRM | Serum | 0 | 37 | CPM; APOB; CADM1; CFH; CP; CTSD; GOLM1; TIMP1 | 8 | Therapeutic |
| (105) | Prostate | Affinity depletion of 7 abundant proteins | Literature | 10 | SID-SRM | Seminal liquid; blood plasma | – | 37 | SNP-L132I | 1 | Prognostic |
| (106) | Thyroid | – | Literature | 21 | LF-SRM; SID-SRM | Tissue | 9 | 27 | S100A6; S100A11; ANXA1; S100A13; S100A4; S100A10; ANXA2 | 7 | Diagnostic; prognostic; therapeutic |
A variety of different targeted proteomic methods were employed and are also described.