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Table 3 Representative examples of BCa biomarker candidates identified by proteomic approaches

From: Clinical proteomic biomarkers: relevant issues on study design & technical considerations in biomarker development

Biomarker identification; Biomarker candidate/panels Verification/Validation Regulation Potential clinical value; Biomarker performance Ref.
Gel-based approaches
2DE , n=24     [178]
Tissue: Western Blot ↑ in both NMIBC and MIBC; Predict cancer progression
6 normal urothelium, 9 NMIBC, 9 MIBC Immunohistochemistry, n=24 ↑ phosphorylation level of cofilin in BCa tissue samples (most prominent in MIBC). Lack of evaluation of biomarker performance.
Cofilin For both experiments, the same material was used as in the discovery phase.
IMAC, 1-SDS-PAGE , n=35 Western Blot    [182]
Urine: Aminopeptidase N, n=108 Aminopeptidase N Biomarker for cancer aggressiveness
Two pools from NMIBC, n1=9, n2=7 Myeloblastin, n=97 ↑ in MIBC  
Two pools from MIBC, n3 = 9, n4=10 ELISA Myeloblastin, Profilin 1 Lack of evaluation of biomarker performance.
Aminopeptidase N, Myeloblastin, Profilin-1, n=82 ↓ in MIBC  
Profilin-1    
  Western Blot, 8 BCa cell line models ↑ in BCa cases, association with stage   [181]
DIGE , n=14 Tissue microarray, n=292 Diagnosis, staging, outcome prognosis
Urine: Primary urothelial cell carcinoma Detection of BCa:
7 BCa (positive cytology), 7 controls (negative cytology) ELISA, n=80  
Reg- 1 Urine: 81.3% sensitivity
32 BCa (positive cytology), 48 Controls 81.2% specificity
(negative cytology)  
Gel-free approaches
  ELISA, n = 166    [179]
  Urine,   
LC-MS/MS , n=20    
Urine: For H2B: n=147, ↑ level of H2B with cancer stage in urine and tissue samples Prediction of disease progression, discrimination of tumor stages
Benign (n=5), pTa, pT1 (n=10), pT2+ (n=5) For NIF-1: n = 158
In both groups urine from benign, NIMB (Ta, Ta) and MIBC (T2+) were included.
histone H2B, NIF-1
↓ level of NIF-1 with cancer stages (not agreement with urinary level) Lack of evaluation of biomarker performance.
Immunohistochemistry, n=32
pTa, pT1, n=23, pT2+ n=9
iTRAQ , n=12 Immunohistochemistry, n=303 ↑ in 4/6 BCa samples in comparison to control (iTRAQ); Prediction of disease progression [180]
Tissue:
6 bladder cancer tissues (4 NMIBC, 2 MIBC) and paired normal tissues;
Inverse correlation to stage and histological grade progression (immunohistochemistry) Lack of evaluation of biomarker performance.
DDX39
CE-MS , n=248 CE-MS, n=130 ↓ regulated in MIBC in comparison to NMIBC Prediction of MIBC: [92]
Urine: Urine, 81% sensitivity
127 BCa patients, 121 Controls Test set: 68 NMIBC and 62 MIBC 57% specificity
4 polypeptide panel
CE-MS , n=79 CE-MS, n=366 Varied; 10 peptides ↑ in BCa;   [93]
Urine: Urine, 12 ↓ in BCa in comparison to control Detection of BCa:
46 BCa patients, 33 Controls (Test set includes healthy controls, patients with non-malignant and malignant urological disorders) 100 % sensitivity
22 polypeptides panel 73% specificity