Table 2 Studies regarding circulating ncRNAs in blood as potential biomarkers for bladder cancer

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]