Table 4.
Circulating and non-circulating miRNAs as BC biomarkers. All the reported miRNAs have been validated on BC patients. For each miRNA, we indicated whether they have a role in diagnosis, prognosis or in prediction of therapy response in BC. For all groups we indicated the biological samples used for the validation, the validation assay, the cohort of data, the main results and the references. This table focused on few examples of single miRNA or miRNA signatures described in the text. GGI=gene expression grade index: TAM=tamoxifen; H= herceptin; N= normal tissue; T= tumor tissues; TNBC= triple negative breast cancer.
| Type of miRNAs | miRNA annotation | Role | Biological Samples | Technique/ cohort |
Results | Ref. |
|---|---|---|---|---|---|---|
| Non-circulating miRNAs | 13 miRNAs (miR-9-1, miR-10b, miR-21, miR-34, miR-29b/102, miR126, miR125a/b1/b2, miR-140as, miR-145, miR-155, miR-194, miR-204, miR-213) | Diagnosis | Tissue | Microarray and northern blot/ 76 BC vs 10 N |
4/13 are downregulated (5 miRNAs are the most constantly deregulated in BC) | 164 |
| 133 miRNAs | Diagnosis | Tissue | Microarray / 99 BC vs 5 N and 33 BC cell lines | 31 miRNAs are associated with tumor subtype or clinical pathological fators | 202 | |
| 15 miRNAs miR-342, miR-299, miR-217, miR-190, miR-135b, miR-218.; miR-520g, miR-377, miR-527-518a, miR-520f-520c; miR-520d, miR-181c, miR-302c, miR-376b, miR-30e |
Diagnosis | Tissue | Microarray / 95 BC vs 17 N | ER+; PR+; HER2/neu+: | 203 | |
| 6 BC-miRNAs signature miR-21 miR-17-5p miR-29b-2 miR-146 miR-155 miR-181b-1 |
Diagnosis | Tissue | Microarray/ 363 T vs 177 N | 31% of the total miRNAs varied among T and N tissues; they identified the most commontly altered miRNAs in solid tumors | 184 | |
|
miR-7, miR-128a, miR-210, and miR-516-3p; miR-210 |
Diagnosis | Tissue | TaqMan / 185 ER+ vs 114 ER- BC |
4-miRNA signature associated with tumor aggressiveness in ER+ BC and miR-210 associated with early relapse in ER- | 204 | |
| let-7c, miR320dmiR567, miR139-5p | Diagnosis | Tissue | Microarray / 42 BC G1 vs 42 BC G3 |
4 miRNA signature | 21 | |
|
let-7a miR-335 |
Diagnosis and prognosis | Tissue | TaqMan/ 60 BC vs 60 N |
Both miRNAs are decreased in BRCA mutant; miR-335 could be used as prognostic marker | 66 | |
| miR-155, miR-493, miR-30e, miR-27a | Diagnosis and prognosis | Tissue | Microarray/ 80 high risk vs 80 low risk | 2 upregulated, 'protective' miRNAs (miR-155, miR-493); 2 downregulated risk-associated miRNAs (miR-30e , miR-27a ) | 205 | |
|
miR-210 miR-148a |
Prognosis | Tissue | qRT-PCR/ 89 ER+ BC +TAM vs 56 N |
miR-210 and miR-148a are associated with relapse free survival; | 206 | |
|
miR-190b miR-339-5p miR-520c-3p /g/h miR-139-3p miR-204 miR-502-5p miR-365 miR-363 miR-7 |
Prediction of therapy response (TAM) | Tissue | Microarray/ 26 patients with recurrence vs 26 patients without recurrence |
miR-7 correlates with tumor grade | 212 | |
|
miR-30c miR-422a miR-30a-3p miR-187 miR-182 |
Prediction of therapy response (TAM) | Tissue | qRT-PCR/ 38 ER+ BC vs 15 BC+TAM |
Higher miR-30a-3p, miR-30c, and miR-182 are associated with treatment benefits | 213 | |
|
miR-21, miR-181b, miR-26a/26b, miR-27b miR-23b, let-7 family, miR-125a-5p/b-5p |
Prediction of therapy response (TAM) | Cell lines and tissue | qRT-PCR/ i) BC cell lines ± ER activation ii) 15 ER+ BC + exemestane and TAM |
All miRNAs are upregulated upon anti-estrogen treatment | 214 | |
| miR-26a, miR-30b, let-7 family, miR-125a/b | Prediction of therapy response (H) | Tissue | Microarray/ 83 BC + H vs adiacent stromal microdissected cells | With SVM technique, they developed a 35 miRNA signature for H treatment response | 216 | |
| Circulating miRNAs | miR-155 | Diagnosis | Serum | qRT-PCR/ 89 BC vs 29 N |
miR-155 is increased, both in primary and metastatic BC | 208 |
| miR-195 | Diagnosis | Blood | qRT-PCR/ 83 BC patients vs 44 N |
miR-195 is increased +19.25 fold | 209 | |
|
miR-29a miR-21 |
Diagnosis and prognosis | Serum | qRT-PCR/ 20 BC sera vs 20 N |
both miRNAs are increased; miR29a correlates with tumor stage | 210 | |
|
miR-16 miR-25 miR-222 miR-324-3 p |
Diagnosis and prognosis | Serum | TaqMan / 48 BC vs 48 N |
All are increased in high risk patients | 211 | |
|
let-7 miR-21 miR-202 |
Diagnosis and prognosis | Blood and serum | RT-PCR/ 136 BC vs 60 non BC |
All miRNAs are increased in BC patients; | 224 | |
|
miR-18b miR-103 miR-107 miR-652 |
Diagnosis, prognosis | Serum | RT-PCR/ 33 primary TNBC vs 33 N | 4 miRNA signature predict tumor relapse and overall survival | 225 | |
| miR-210 | Prediction of therapy response (H) | Plasma | TaqMan / 18 BC+ H vs 11 not responding BC |
miR-210 is higher in patients with residual BC (+2 fold) | 222 | |
| miR-155 | Prediction of therapy response (taxane) | Serum | RT-PCR/ 103 BC+taxane vs 55 N |
miR-155 expression correlates with the treatment course | 223 |