New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins
Abstract
1. Introduction
2. Urinary Proteins for Bladder Cancer Diagnosis
3. Urinary micro RNAs for Bladder Cancer Diagnosis
4. Conclusions
Supplementary Materials
Funding
Conflicts of Interest
References
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Abbreviation | Name | Cellular Function and Pathway | Concentration in BC Urine Samples |
---|---|---|---|
A1AT/(SERPINA1) | Serpin family A member 1 | Complement and coagulation cascades [15]. | Both ELISA and Multi-array assay revealed that candidates including A1AT could discriminate BC patients from controls, NMIBC from MIBC [16]. Strongly correlated with urinary hemoglobin (Spearman’s correlation coefficient >0.8), so the increase in concentration in BC patients’ urine samples may be due to hematuria [11]. |
ANG | Angiogenin | Angiogenesis [17]. | Urinary concentrations of ANG were significantly elevated in subjects with BC compared to controls [18]. Both ELISA and Multi-array assay revealed that candidates including ANG could discriminate BC patients from controls, NMIBC from MIBC [16]. |
Apo-A1 | Apolipoprotein A1 | Lipid metabolism and transport [19]. | Increased in urine samples of aggressive Bladder transitional cell carcinoma (BTCC) compared to low malignant BTCC [5]. Western blot analysis and ELISA assays also revealed that candidates including Apo-A1 levels in urine samples of BC patients were significantly elevated [4]. |
APOE | Apolipoprotein E | Transport of cholesterol and other lipids [20] | Urinary concentrations of APOE were significantly elevated in subjects with BC compared with controls but diagnostic performance of APOE as a single biomarker was not sufficient [11,21]. APOE levels were significantly increased in high compared to low grade tumors as well as in MIBC compared to NMIBC, both ELISA and Multi-array assay revealed that APOE could discriminate BC patients from controls [16,18]. |
BTA/hCFHrp | complement factor H-related protein | Involved in complement regulation. | Urinary concentrations of BTA were significantly elevated in subjects with BC [10,11,22,23,24,25]. |
CA9 | carbonic anhydrase 9 | Involved in pH regulation, control of cell proliferation and transformation [26]. There are also studies advocating axiom. | Urinary concentrations of CA9 were significantly elevated in subjects with BC [11,24]. But some studies advocating the opposite [18]. |
CCL18 | C-C motif chemokine ligand 18 | Involved in immunoregulatory and inflammatory processes [27]. | Urinary concentrations were significantly elevated in subjects with BC [22]. The concentrations of CCL18 in urine samples are correlated with hemoglobin, so the increase in concentration in BC patients’ urine samples may be due to hematuria [11]. |
CD44 | CD44 antigen (Epican) | Cell-surface glycoprotein, involved in cell–cell interactions, cell adhesion and migration [28]. | Urinary concentrations of CD44 were significantly decreased in subjects with BC [11]. CD44 improved the prediction power of CCL18, PAI-1 (AUC = 0.938) [22]. |
IL-8 | Interleukin-8 | Chemotactic factor, released from several cell types in response to an inflammatory stimulus [29]. | Group of proteins, including IL-8, had significantly higher expression in BC subjects, IL-8 was the most consistent one, multivariate regression analysis revealed that only IL-8 was an independent factor for the detection of BC [25]. Urine IL-8 levels were significantly increased in high compared to low-grade tumors as well as in MIBC compared to NMIBC. IL8 could discriminate BC patients from controls, low grade BC from high grade BC, NMIBC from MIBC [18]. |
MMP-10 | Stromelysin-2/Matrix metalloproteinase-10 | Breakdown of extracellular matrix [30]. | Significantly higher expression was detected in urine samples of bladder cancer patients compared to healthy controls [11,18]. Both ELISA and Multi-array assay revealed that MMP-10 could discriminate BC patients from controls, low grade BC from high grade BC, NMIBC from MIBC [16]. |
MMP-9 | Matrix metalloproteinase-9 | Involved in breakdown of extracellular matrix and in leukocyte migration [31]. | Significantly higher expression was detected by ELISA in urine samples of bladder cancer patients compared to healthy controls [11]. Both ELISA and Multi-array assay revealed that MMP-9 could discriminate BC patients from controls, NMIBC from MIBC [16]. Biomarker levels were also compared with respect to tumor grade and stage. IL-8, MMP-9, PAI-1 and APOE were significantly increased in high compared to low grade tumors as well as in MIBC compared to non-MIBC [18]. |
OPN (SPP1) | Osteopontin | Appears to be involved in tumorigenesis, metastasis, Cell-matrix interaction and type 1 immunity [32]. | Urinary concentrations of OPN were significantly elevated in subjects with BC [11]. |
PAI-1 (SERPINE1) | Plasminogen activator inhibitor-1 | Inhibitor of fibrinolysis. High expressions are associated with thrombophilia [33]. | Urinary concentrations of CCL18, PAI-1, and BTA were significantly elevated in subjects with BC [22]. Urinary concentrations of 14 biomarkers including PAI-1 were significantly elevated in subjects with BC [11]. Both ELISA and Multi-array assay revealed that PAI1 could discriminate BC patients from controls, low grade BC from high grade BC, NMIBC from MIBC, PAI-1 was the most accurate single biomarker for BC followed closely by urinary IL8 [16]. |
PTX3 | Pentraxin 3 | Expressed in numerous tissues, such as monocytes, dendritic cells, takes role in inflammation [34]. | Urinary concentrations of PTX3 were significantly elevated in subjects with BC [11]. PTX concentration in urine samples analyzed by ELISA but no significant difference found between BC and controls [23]. |
Scd-1 | Syndecan-1 | Involved in cytoskeleton regulation and exosome biogenesis [35]. | Elevated in the urine samples of BC patients but results were not consistent. Any significant association between cancer, control or stage found [11,16,36]. |
sFAS | Soluble Fas | Prevents apoptosis induction, and enhances the immunosuppressive effects of tumors [37]. | The urinary sFas levels were significantly higher in the patients with UC than in those without cancer [37], significantly elevated in the NMIBC cases with a higher stage or grade or high-risk group category than in those with a lower stage or grade or low-risk group category [38]. |
VEGF | Vascular endothelial growth factor | Active in angiogenesis, vasculogenesis and endothelial cell growth [39]. | Urinary concentrations significantly elevated in subjects with BC [11]. VEGF was the most accurate urinary biomarker [24] and could discriminate BC patients from controls, NMIBC from MIBC [16]. |
let-7b | miR-27b | miR-125b | miR-182 | miR-222 | miR-515 |
let-7i | miR-29a | miR-126-5p | miR-183 | miR-223 | miR-520e |
miR-1 | miR-29a-3p | miR-133a | miR-187 | miR-302d | miR-545 |
miR-7-5p | miR-34a | miR-133b | miR-191 | miR-325 | miR-556 |
miR-9-3 | miR-92a | miR-134 | miR-192 | miR-328 | miR-589 |
miR-10a | miR-93 | miR-135b | miR-193a-3p | miR-328 | miR-616 |
miR-10b | miR-96 | miR-137 | miR-200a | miR-335 | miR-618 |
miR-15a | miR-99a | miR-140-5p | miR-200a-3p | miR-338-3p | miR-873 |
miR-15b | miR-100 | miR-141 | miR-200b | miR-375 | miR-890 |
miR-16 | miR-101 | miR-142-3p | miR-200c | miR-377 | miR-892a |
miR-18a | miR-106b | miR-143 | miR-203 | miR-423-5p | miR-923 |
miR-18a-3p | miR-122-3p | miR-145 | miR-204 | miR-424 | miR-940 |
miR-21 | miR-122-5p | miR-146a-5p | miR-205 | miR-429 | miR-1207-5p |
miR-22-3p | miR-124-2 | miR-148a | miR-210 | miR-451a | miR-1224 |
miR-24-1 | miR-124-3 | miR-149 | miR-211 | miR-452 | miR-1224-3p |
miR-25 | miR-1255b | miR-152 | miR-212 | miR-483-5p | miR-1225-5p |
miR-26a | miR-1255b-5p | miR-155 | miR-214 | miR-505 | |
miR-27a | miR-125a | miR-156 | miR-221 | miR-509 |
Validated Target Gene | miRNA |
---|---|
BCL2 | hsa-miR-100-5p hsa-miR-122-5p hsa-miR-155-5p hsa-miR-29a-3p hsa-miR-429 hsa-miR-21-5p |
CCND1 | |
CCND2 | |
CDK6 | |
CDKN1A | |
ERBB2 | |
IGF1R | |
MYB | |
MYC | |
PTEN | |
RECK | |
RHOA | |
SMAD4 | |
SP1 | |
TP53 | |
VEGFA | |
WEE1 |
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Share and Cite
Güllü Amuran, G.; Peker Eyuboglu, I.; Tinay, I.; Akkiprik, M. New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins. Med. Sci. 2018, 6, 113. https://doi.org/10.3390/medsci6040113
Güllü Amuran G, Peker Eyuboglu I, Tinay I, Akkiprik M. New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins. Medical Sciences. 2018; 6(4):113. https://doi.org/10.3390/medsci6040113
Chicago/Turabian StyleGüllü Amuran, Gökçe, Irem Peker Eyuboglu, Ilker Tinay, and Mustafa Akkiprik. 2018. "New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins" Medical Sciences 6, no. 4: 113. https://doi.org/10.3390/medsci6040113
APA StyleGüllü Amuran, G., Peker Eyuboglu, I., Tinay, I., & Akkiprik, M. (2018). New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins. Medical Sciences, 6(4), 113. https://doi.org/10.3390/medsci6040113