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

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