Table 3.
Table presenting data for proteomics biomarkers.
| Biomarker | Purpose | Number of Patients | Method | Diagnostic Value | Prognostic Value | Predictive Capacity | Type of Study | Reference |
|---|---|---|---|---|---|---|---|---|
| APOA1 | prognostic | n = 258 (BCa = 108; control group = 150) | Genomic DNA was extracted from the blood and tumour tissues of all patients using the phenol chloroform method and DNA extraction kit (Zymo Research Corporation, Irvine, CA, USA). PCR was conducted using DNTP (Sigma-Aldrich, St. Louis, MO, USA), 10 mMdTTP primers (Sigma-Aldrich, St. Louis, MO, USA) and Taq DNA polymerase (Biotools, Madrid, Spain). PCR-RFLP was performed using a restriction endonuclease enzyme (New England Biolabs, NEB, England). APOA1 concentrations were measured using standard source ELISA kit (Thermo Scientific, Waltham, MA, USA). | n/a | BCa progression | AUC = 0.889 | retrospective | [38] |
| CDHR2 | Prognostic and surveillance | n = 40 (n = 8 no history or evidence of BCa, n = 4 geneal urinary system diseases, n = 16 BCa prior to surgery, n = 12 BCa after surgical removal of the tumour) | Urine samples of 40 patients obtained pre- and postoperatively. iTRAQ reagent kit (8plex, Applied Biosystems, Bedford, MA, USA) was used to quantify proteins in the urine. Q-Exactive mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA) was used to analyse the samples which then were validated with western blot. | n/a | Postoperative non-recurrence probability | No data | retrospective | [31] |
| HSP27 | n/a | High expression is associated with BCa progression | No data | |||||
| HNRNPA2B1 | n/a | Postoperative non-recurrence probability | No data | |||||
| BTA | Diagnostic and prognostic | n = 157 (BCa = 61, NMIBC: LG = 30, HG = 15; MIBC: hG = 16; UTUC = 44; control group = 52) | Cytology urine of 157 patients was performed and interpreted by pathologists. NMP and BTA-stat were measured by NMP22 (Alere INC., Waltham, MA, USA) and BTA-stat assays (Polymedco CDP, LLC., NY, USA). BTA was measured by chemiluminescence (Pergrande, Beijing, China), and ELISA for survivin (R&D systems, MN, USA). Data analysis performed with SPSS v.19.0 (IBM Corp., Armonk, NY, USA) and GraphPad prism7 (GraphPad Software Inc., Sand Diego, CA, USA). |
BCa vs. UTUC differentiation | BCa survival | AUC = 0.84, PPV = 82%, NPV = 72%, Se. = 74%, Sp. = 81% | retrospective | [33] |
| BTA-stat | AUC = 0.67, PPV = 70%, NPV = 64%, Se. = 69%, Sp. = 63% | |||||||
| NMP22 | AUC = 0.69, PPV = 77%, NPV = 62%, Se. = 59%, Sp. = 79% | |||||||
| Survivin | AUC = 0.84, PPV = 84%, NPV = 75%, Se. = 74%, Sp. = 81% | |||||||
| PD-L1 | diagnostic |
n = 122 (group 1 = 20, NMIBC: LG = 7, HG = 9; MIBC: HG = 4; group 2 = 63, NMIBC: LG = 10, HG = 21; MIBC: LG = 3, HG = 29; group 3 = 39, NMIBC: LG = 17, HG = 30; MIBC: LG = 3, HG = 33) |
Quantikine ELISA for Human/Cynomolgus Monkey PD-L1/B7-H1 Immunoassay from R&D Systems (Catalog Number DB7H10) was used to inspect the urine samples of 122 patients. Data analysis was performed with SAS software v 9.4 (SAS institute Inc., Cary, NC, USA). | BCa detection | AUC = 0.74, PPV = 92%, NPV = 47%, Se. = 53%, Sp. = 90% | retrospective | [34] | |
| ADXBLADDER | prognostic | n = 629 (No recurrent BCa = 550, recurrent BCa = 79) | ADXBLADDER test was performed on urine samples of 629 patients. Data analysis was performed with Stata 12.1 (StataCorp,.College Station, TX, USA) | BCa recurrence prediction | AUC = 0.56, PPV = 17.5%, NPV = 99.15%, Se. = 66.7%, Sp. = 76.0% | prospective | [35] | |
| ANG | prognostic | n = 64 | Urine samples of 64 patients were tested with multiplex bead-based immunoassay (Oncuria™) from R&D Systems Inc (Minneapolis, MN, USA). Data analysis was performed with SAS software version 9.3 (SAS Institute Inc., Cary, NC, USA). | Treatment response, recurrence | AUC = 0.7444, PPV = 41.2%, NPV = 91.5%, Se. = 63.6%, Sp. = 81.1% | prospective | [36] | |
| CA9 | AUC = 0.6878, PPV = 30.4%, NPV = 90.2%, Se. = 63.8%, Sp. = 69.8% | |||||||
| MMP10 | AUC = 0.7238, PPV = 32%, NPV = 92.3%, Se. = 72.7%, Sp. = 67.9% |
Abbreviations: AUC—Area under the ROC Curve, n—number of patients participating in study, HG—high grade, LG—low grade, BCa—bladder cancer, PCR—polymerase chain reaction, PCR-RFLP—Restriction fragment length polymorphism PCR, PPV—positive predictive value, NPV—negative predictive value, Se.—sensitivity, Sp.—specificity, APOA1—Apolipoprotein A1, CDHR2—Cadherin Related Family Member 2, HSP27—heat shock protein beta-1, HNRNPA2B1—Heterogeneous Nuclear Ribonucleoprotein A2/B1, BTA—Bladder Tumour Antigen, NMP22—Nuclear Matrix Protein-22, PD-L1—Programmed Cell Death 1 Ligand 1, ANG—Angiogenin, CA9—Carbonic Anhydrase 9, MMP10—Matrix Metallopeptidase 10.