Table 4.
Diagnostic performance of tumor tissue proteome/TIF markers validated in blood.
| First Author, Year, [Ref] | Proteins | Sensitivity (95%CI) % | Specificity (95%CI) % | Area under the Curve (95%CI) | Method | Validation | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CEA | CA19-9 | ACVR2B | AZGP1 | GDF15 | LRG1 | S100A9 | MAPKAP3 | TIMP1 | PIM1 | Others | ||||||
| Tumor Tissue Proteome Combination Marker Studies | ||||||||||||||||
| Broll, 2001 [56] | x | VEGF | 62 (53–71) | 85 (74–93) | - | ELISA | No | |||||||||
| Alberthsen, 2006 [60] | HNP1, HNP2, HNP3 | 80 (72–87) | 53 (35–70) | - | ELISA | No | ||||||||||
| Yoneda, 2009 [41] | x | x | Cystatin SN | 63 (55–71) | 90 (76–97) | - | ELISA | No | ||||||||
| Kijanka, 2010 [62] | ZNF700, TSLC1, LASS5, p53, TCF3, SNP29, ZNF638, ICLN, ZNF346, AOPJ75, HMGB1, BAC85857 | 84 (70–93) | 80 (64–91) | - | PrA | SS | ||||||||||
| Xie, 2010 [27] # | A1AT, CTSD | 100 (92–100) | 97 (87–100) | - | WB | No | ||||||||||
| Hamelin, 2011 [61] | x | x | HSP60 | 47 (38–57) | 90 (82–95) | 0.77 (0.70–0.84) | ELISA | SS | ||||||||
| Kuo, 2011 [39] | x | PLSCR1 | 85 (73–93) | 48 (34–62) | 0.80 | WB | No | |||||||||
| Matsubara, 2011 [42] | x | Adipophilin | 31 (15–52) | 95 (88–99) | 0.783 | RPPM | SS | |||||||||
| Wang, 2013 [25] | x | Kininogen-1 | 22 (16–30) | 93 (85–97) | - | ELISA | CV | |||||||||
| Jiang, 2014 [23] | DC-SIGN, DC-SIGNR | 99 (96–100) | 95 (89–98) | 0.989 | ELISA | No | ||||||||||
| Xue, 2014 [29] | x | x | x | 74 (65–82) | 73 (57–86) | 0.805 (0.738–0.872) | ELISA | LOOCV | ||||||||
| Surinova, 2015 [58] | x | x | CP, PON1, SERPINA3 | 70 (63–76) | 79 (67–88) | 0.84 (0.75–0.92) * | SRM | TFCV | ||||||||
| Wang Y, 2016 [32] | x | TUBB5 | 63 (36–85) | 81 (54–96) | 0.74 | MRM | No | |||||||||
| Xie, 2016 [34] | CELA1, CEL2A, CTRL, TRY2 | 87 (70-96) | 83 (65-94) | 0.90 (0.83–0.98) | MRM | No | ||||||||||
| Tumor Tissue Proteome Individual Marker Studies | ||||||||||||||||
| Roessler, 2005 [57] |
x |
NNMT | 51 (41–61) 39 (30–49) |
95 (92–97) 95 (92–97) |
0.84 0.78 |
ELISA | No | |||||||||
| Kim, 2009 [47] |
x |
x |
S100A8 | 41 (30–53) 44 (33–56) 22 (13–33) |
95 (76–100) 95 (76–100) 100 (94–100) |
0.91 0.89 0.78 |
WB | No | ||||||||
| Ji, 2010 [45] |
x |
ESM-1 | 99 (95–100) 48 (38–58) |
73 (62–82) 99 (94–100) |
0.94 0.733 |
ELISA | No | |||||||||
| Han, 2011 [21] | STOML2 | 71 (59–81) | 63 (51–74) | 0.77 | ELISA | No | ||||||||||
| Fijneman, 2012 [63] |
x |
CHI3L1 | 75 (35–97) 38 (9–76) |
89 (74–97) 100 (90–100) |
0.81 0.86 |
ELISA | No | |||||||||
| Hosono, 2012 [44] A | TNF-R1 | 93 (84–98) | 82 (65–93) | - | ELISA | No | ||||||||||
| Yao, 2012 [30] |
x |
EFEMP2 | 83 (75–89) 63 (54–72) |
93 (85–98) 77 (66–86) |
0.923 (0.885–0.961) 0.728 (0.659–0.797) |
ELISA | SS | |||||||||
| Ji, 2013 [22] | x |
PEDF PRDX2 |
100 (99–100) 34 (29–39) 87 (83–90) |
79 (69–87) 96 (89–99) 51 (40–62) |
- | ELISA | SS | |||||||||
| Niewiarowska, 2014 [64] | x | 67 (51–81) | 67 (45–85) | 0.666 | ELISA | No | ||||||||||
| Sole, 2014 [55] § | COL10A1 | 63 (52–74) | 85 (75–92) | 0.75 | ELISA | SS | ||||||||||
Note: #: The sensitivity and specificity values are for tissue array based validation and not serum based; *: The confidence interval for area under the curve in this study was reported for 99% CI; §: The sensitivity and specificity values are for CRC or Adenoma cases; A: The sensitivity and specificity values are for only Adenoma cases and not CRC; -: means not specified by the study; x: this type of protein was identified by the study. Abbreviation: A: Adenoma; CV: Cross-validation method; ELISA: Enzyme-linked immunosorbent assay; LOOCV: Leave-one-out cross validation; MRM: Multiple reaction monitoring; PrA: Protein Array; RPPM: Reverse phase protein microarray; SRM: Selected reaction monitoring used in tandem mass spectrometry; SS: Split Sampling method; TFCV: Ten-fold Cross validation; WB: Western Blot. Abbreviations for proteins: A1AT: α1 antitrypsin; ACVR2B—Activin receptor type-2B; AOPJ75: KIAA0310 protein; AZGP1: Zinc-α-2-glycoprotein; BAC85857: Unnamed protein product; CA 19-9: Carbohydrate antigen; CEA: Carcinoembryonic antigen 19-9; CELA1: chymotrypsin-like elastase 1; CELA2: chymotrypsin-like elastase 2A; CHI3L1: Chitinase-3-like protein 1; COL10A1: Collagen alpha-1(X) chain; CP: Ceruloplasmin; CTRL: chymopasin; CTSD: Cathepsin D; DC-SIGN: Dendritic cell-specific ICAM-3 grabbing nonintegrin; DC-SIGNR: DC-SIGN-related protein/L-SIGN, CD209L; GDF15: Growth/differentiation factor 15; EFEMP2: EGF-containing fibulin-like extracellular matrix protein 2; ESM-1: Endothelial cell-specific molecule-1; HMGB1: High mobility group protein B1; HNP1: Human neutrophil peptide 1; HNP2: Human neutrophil peptide 2; HNP3: Human neutrophil peptide 3; HSP60: Heat shock protein 60; ICLN: Methylosome subunit plCln; LASS5: Longevity assurance gene homologous 5; LRG1: Leucine-rich alpha-2-glycoprotein; MAPKAPK3: Mitogen-activated protein kinase-activated protein kinase 3; NNMT: Nicotinamide N-Methyltransferase; PEDF: Pigment epithelium derived factor; PIM1: Serine/threonine-protein kinase pim-1; PLSCR1: phospholipid scramblase 1; PON1: Serum paraoxonase/arylesterase 1; PRDX2: Peroxiredoxin 2; S100A8/A9: S100 calcium-binding protein A8/A9; SERPINA3: Serpin peptidase inhibitor clade A; SNP29: Synaptosomal-associated protein 29; STOML2: Stomatin like 2; TCF3: E2A immunoglobulin enhancer-binding factor E12/E47; TIMP1: Tissue inhibitor of metalloproteinases 1; TNF-R1: Tumor necrosis factor receptor 1; TRY2: trypsin 2; TSLC1: Tumour suppressor in lung cancer I; TUBB5: tubulin beta-5 chain; VEGF: Vascular endothelial growth factor; ZNF346: Zinc finger protein 346; ZNF638: Zinc finger protein 638; ZNF700: Zinc finger protein 700.