Table 2.
Studies regarding circulating ncRNAs in blood as potential biomarkers for bladder cancer
| ncRNA | Authors (year) | Sample type | Significant miRNA expression | Study design | Detection method and reference method | Clinically relevant findings | Refs. |
|---|---|---|---|---|---|---|---|
| miRNA | |||||||
| Feng et al. (2014) | Plasma | miR-99a↓ |
• 50 patients • 50 controls |
• RT-qPCR • RNU6 |
Diagnostic marker: no information concerning diagnostic accuracy | [76] | |
| Feng et al. (2014) | Plasma | • miR-19a↑ |
• 50 patients • 50 controls |
• RT-qPCR • RNU6 |
Diagnostic marker: no information concerning diagnostic accuracy | [77] | |
| Adam et al. (2013) | Plasma |
• miR-200b↑ • miR-33b↓ • miR-92b↓ |
• 20 patients • 18 controls |
• RT-qPCR • RNU6 |
• 89% accuracy for detecting BC • 92% accuracy for distinguishing invasive BC from other cases • 100% accuracy for distinguishing MIBC from controls • 79% accuracy for three-way classification between MIBC, NIMBC, and controls |
[78] | |
| Wang et al. (2019) | Serum | • miRNA‑373↑ |
• 55 patients • 45 controls |
• RT-qPCR • RNU6 |
Diagnosis of BC (AUC = 0.847) | [79] | |
| Motawi et al. (2016) | Plasma |
• miR-92a↓ • miR-100↓ • miR-143↓ |
• 70 patients • 62 controls |
• RT-qPCR • RNU6 |
• Diagnosis of BC with miR-92a (AUC = 0.940, DS = 97.1%, DSp = 76.7%) • Diagnosis of BC with miR-100 (AUC = 0.820, DS = 90%, DSp = 66.7%) • Diagnosis of BC with miR-143 (AUC = 0.915, DS = 78.6%, DSp = 93.3%) |
[80] | |
| Yang et al. (2015) | Serum | • miR-210↑ |
• 168 patients • 104 controls |
• RT-qPCR • RNU6 |
• Diagnosis of BC (AUC = 0.898, DS = 97.6%, DSp = 69.2%) • Prognostic marker: monitor tumor dynamics |
[81] | |
| Fang et al. (2016) | Plasma | • miR-205↑ |
• 89 patients • 56 controls |
• RT-qPCR • RNU6 |
• Diagnosis of BC (AUC = 0.950, DS = 76.4%, DSp = 96.4%) • Differentiation of NIMBC from MIBC (AUC = 0.668, DS = 57.1%, DSp = 77.0%) |
[82] | |
| Du et al. (2015) | Plasma |
• miR-497↓ • miR-663b↑ |
• Discovery: pools of 10 patients and 10 controls • Validation: training set with 56 patients and 60 controls, and test set with 109 patients and 115 controls |
• Discovery: TaqMan array • Validation: RT-qPCR |
Diagnosis of cancer with the two combined miRNAs (AUC = 0.711, DS = 69.7%, DSp = 69.6%) | [83] | |
| Lian et al. (2018) | Serum | • miR-409-3p↓ |
• Discovery: 140 patients, 139 healthy controls • Validation: 140 patients, 139 controls |
• Discovery: TaqMan array • Validation: RT-qPCR |
Diagnostic marker: no information concerning diagnostic accuracy | [84] | |
| Jiang et al. (2015) | Serum |
• miR-152↑ • miR-1486-3p↑ • miR-3187-3p↓ • miR-15b-5p↓ • miR-27a-3p↓ • miR-30a-5p ↓ |
• Discovery: pooled samples from 10 patients with NMIBC, 10 patients with MIBC, 10 healthy controls • Validation: training set 120 patients and 120 controls, and validation set 110 patients and 110 controls |
• Discovery: sequencing • Validation: RT-qPCR |
• Diagnosis of cancer with all miRNAs (AUC = 0.899, DS = 80%, DSp = 89%) • Differentiation of NIMBC from MIBC (AUC = 0.841, DS = 90%, DSp: 66.4%) • Prognostic marker set miR-152 and miR-3187-3p: recurrence-free survival for NIMBC, not for MIBC |
[85] | |
| Jiang et al. (2016) | Serum |
• miR-422a-3p (↑ in NMIBC, ↓in MIBC) • miR-486-3p↓ • miR-103a-3p (↑ in NMIBC, ↓in MIBC) • miR-27a-3p↓ |
• Discovery: pooled samples from 6 patients with NMIBC, 6 patients with MIBC, 6 healthy controls • Validation: training set 40 MIBC, 40 NMIBC, and 40 controls, and validation set 90 MIBC and 168 NMIBC |
• Discovery: sequencing • Validation: RT-qPCR |
• Diagnosis of cancer with the four combined miRNAs (training set: AUC = 0.894, validation set: AUC = 0.880) • Prognostic marker: miR-486-3p and miR-103a-3p were associated with OS of MIBC |
[86] | |
| Usuba et al. (2019) | Serum |
• miR-6087↓ • miR-6724-5p↑ • miR-3960↓ • miR-1343-5p↓ • miR-1185–1-3p↑ • miR-6831-5p↑ • miR-4695-5p↓ |
• Discovery: 196 patients with BC, 50 controls, 240 other types of cancers • Validation set: 196 patients with BC, 50 controls, 240 other types of cancers |
• Discovery: TaqMan array • Validation: RT-qPCR |
Diagnosis of cancer with the seven combined miRNAs (AUC = 0.97, DS = 95%, DSp = 87%) | [87] | |
| LncRNA | |||||||
| Duan et al. (2016) | Serum |
• lncRNA-MEG↓ • lncRNA- SNHG16↑ • lncRNA-MALAT1↑ |
• Discovery: pooled samples from 80 patients with BC and 80 healthy controls • Validation: training set 120 patients with BC, 68 patients with benign disease, 52 healthy controls, validation set 100 patients with BC, 52 patients with benign disease, 48 healthy controls |
• RT-qPCR • GAPDH |
• Diagnosis of cancer with three miRNAs (AUC = 0.899, DS = 80%, DSp = 89%) • Prognostic marker: low expression of MEG3 was associated with poor recurrence-free survival |
[90] | |
| Luo et al. (2019) | Plasma | • lncRNA CASC11↑ |
• 89 patients • 62 controls |
• RT-qPCR • RNU6 |
Diagnosis of BC (AUC = 0.899) | [91] | |
| Zhou et al. (2020) | Serum | • lncRNA LUCAT1↑ |
• 30 patients • 30 controls |
• RT-qPCR • GAPDH |
Diagnostic marker: no information concerning diagnostic accuracy | [92] | |
| Li et al. (2019) | Plasma | • lncRNA TUC338↑ |
• 56 patients • 56 controls |
• RT-qPCR • 18S |
Diagnosis of BC (AUC = 0.924) | [93] | |
| Zhang et al. (2020) | Serum | • lncRNA PCAT6↑ |
• 106 patients • 106 controls |
• RT-qPCR • GAPDH |
• Diagnosis of BC (AUC > 8.0) • Prognostic marker: high expression of lncRNA PCAT6 was associated with poor OS and PFS |
[94] | |
| circRNA | |||||||
| Pan et al. (2019) | Serum |
• circ-FARSA↑ • circ-SHKBP1↑ • circ-BANP↑ |
• 70 patients • 70 controls |
• RT-qPCR • β-actin |
• Diagnosis of cancer with combined lncRNA UCA1 and circSHKBP1 (AUC = 0.804) • Combined circFARSA and circBANP distinguishing recurrent from non-recurrent patients (AUC = 0.737) |
[95] | |
| Chi et al. (2019) | Serum | • hsa_circ_0000285↓ |
• 197 patients • 97 controls |
• RT-qPCR • β-actin |
• Diagnostic marker: no information concerning diagnostic accuracy • Treatment monitoring: low expression of hsa_circ_0000285 was associated with poor chemosensitivity • Prognostic marker: low expression of hsa_circ_0000285 was associated with poor survival rate |
[96] | |
| Xu et al. (2018) | Blood | • circPTK2↑ |
• 40 patients • 40 controls |
• RT-qPCR • GAPDH |
Diagnostic marker: no information concerning diagnostic accuracy | [97] |
ncRNA non-coding RNA, miRNA microRNA, circRNA circular RNA, lncRNA long non-coding RNA, BC bladder cancer, MIBC muscle-invasive bladder cancer, NMIBC non-muscle-invasive bladder cancer, AUC area under the receiver operating characteristics curve, DS diagnostic sensitivity, DSp diagnostic specificity, RT-qPCR reverse-transcription quantitative polymerase chain reaction. ↑ upregulated, ↓ downregulated