Table 1.
miRNA signatures in blood for early detection of BC
| miRNA(s) | Patient cohort | Sample | Methodology | Clinical observation | Reference |
|---|---|---|---|---|---|
| let-7b | 102 BC cases, 26 benign breast disease cases, and 37 healthy controls | Serum (pre- and post-surgery [34 only]) | TaqMan qRT-PCR (Thermo Fisher Scientific) | Higher levels of let-7 separate BC from benign disease and normal breast. | 125 |
| miR-1, miR-92a, miR-133a, miR-133b | Training set: 32 BC cases and 22 healthy controls Validation set: 132 BC cases and 101 healthy controls |
Serum (and matched frozen tissue) | SYBR green qRT-PCR (Exiqon) | Changes in these miRNAs are the most significant out of 20 miRNA found to be informative for early disease detection. | 126 |
| miR-10b, miR-21, miR-125b, miR-145, miR-155, miR-191, miR-382 | 61 BC cases (Stage I–II [44.3%] vs Stage III [55.7%]) and ten healthy controls | Serum | TaqMan qRT-PCR (Thermo Fisher Scientific) | miRNA changes separate BC cases from controls. | 127 |
| miR-15a, miR-18a, miR-107, miR-133a, miR-139-5p, miR-143, miR-145, miR-365, miR-425 | Training set: 48 early-stage ER+ cases (LN− [50%] vs LN+ [50%]) and 24 age-matched healthy controls Validation set: 60 early-stage ER+ cases (LN− [50%] vs LN+ [50%]) and 51 healthy controls |
Serum | SYBR green qRT-PCR (Exiqon) | miRNA changes separate BC cases from controls. | 128 |
| miR-18a, miR-19a, miR-20a, miR-30a, miR-103b, miR-126, miR-126,* miR-192, miR-1287 | 20 BC cases and 30 healthy controls | Serum (samples were pooled) | SOLiD sequencing | miRNA changes separate BC cases from controls. | 129 |
| miR-18a, miR-181a, miR-222 | Training set: 410 participants in sister study (205 eventually developed BC and 205 stayed cancer-free) Validation set: five BC cases and five healthy controls |
Serum | Affymetrix arrays (Discovery study); SYBR green qRT-PCR (Qiagen NV) | miRNAs with highest changes between participants that developed cancer and those who stayed cancer-free. Signature did not validate in independent cohort. | 130 |
| miR-19a, miR-24, miR-155, miR-181b | 63 early-stage BC cases and 21 healthy controls | Serum (pre- and post-surgery, and after first cycle of adjuvant treatment) | TaqMan qRT-PCR (Thermo Fisher Scientific) | miRNA changes separate BC cases from controls. | 29 |
| miR-21 | 89 BC cases (ER+ [77.6%] vs ER− [22.4%]; Stage I–II [55%] vs Stage III–IV [45%]) and 55 healthy controls | Serum | SYBR green qRT-PCR assay (Hoffman-La Roche Ltd) | Increased circulating levels of miR-21 in BC cases. | 131 |
| miR-21, miR-92a | 100 primary BC patients and 20 healthy controls | Serum (and matching tissue) | SYBR green qRT-PCR assay (Takara Bio Inc.) | miRNA changes separate BC cases from controls. | 132 |
| miR-27a, miR-30b, miR-148a, miR-451 | 129 BC cases and 29 healthy controls | Serum | TaqMan qRT-PCR (Thermo Fisher Scientific) | miRNA changes separate BC cases from controls. | 133 |
| miR-30a | 100 BC cases (ER+ [77%] vs ER− [23%]; LN− [69%] vs LN+ [31%]; Stage I–II [77%] vs Stage III–IV[17%]) and 64 age-matched healthy controls | Plasma (pre- and post-surgery) | TaqMan qRT-PCR (Thermo Fisher Scientific) | Decreased circulating levels of miR-30a in BC cases. | 134 |
| miR-92b,* miR-568, miR-708* | 20 BC cases before surgery (ER+ [60%] vs ER− [40%]; Stage I–II [85%] vs Stage III–IV [15%]), 20 BC cases after surgery (ER+ [75%] vs ER− [25%]; Stage I–II [95%] vs Stage III–IV [5%]), ten cases with other cancer types and 20 healthy controls | Plasma | Illumina miRNA arrays | miRNA changes separate BC cases specifically (not present in other cancer types) from controls. | 26 |
| miR-107, miR-148a, miR-223, miR-338-3p | 24 ER+ early-stage BC patients (LN− [50%] vs LN+ [50%]) and 24 age-matched healthy controls | Serum (pre- and post-surgery) | SYBR green qRT-PCR (Exiqon) | miRNA changes separate ER+ BC cases from controls. | 28 |
| miR-127-3p, miR-148b, miR-376a, miR-376c, miR-409-3p, miR-652, miR-801 | Training set: 127 BC cases (ER+ [81.1%] vs ER− [19.1%]; LN− [59%] vs LN+ [41%]; Stage I–II [75.5%] vs Stage III–IV [24.5%]) and 80 healthy controls Validation set: 120 BC cases (ER+ [82.5%] vs ER− [17.5%]; LN− [59.1%] vs LN+ [40.9%]; Stage I–II [78.3%] vs Stage III–IV [21.7%]), 30 benign breast disease cases, and 60 healthy controls |
Plasma | TaqMan qRT-PCR (Thermo Fisher Scientific) | miRNA signature separates BC cases from healthy controls. Only changes in miR-127-3p, miR-376a, miR-376c, and miR-409-3p separate BC cases from benign breast disease. | 135 |
| miR-133a, miR-148b | Training set: 52 early-stage BC cases, 35 DCIS cases and 35 healthy controls Validation set: 50 early-stage patients and 50 healthy controls |
Plasma | SYBR green qRT-PCR (Exiqon) | miRNA changes separate BC cases from controls. | 27 |
| miR-138 | 83 BC cases (ER+ [50.6%] vs ER− [48.4%]; Stage I–II [85.5%] vs Stage III [14.5%]) and 83 healthy controls | Blood | TaqMan qRT-PCR (Thermo Fisher Scientific) | Higher circulating levels of miR-138 separate ER+ BC cases (but not ER− cases) from controls. | 136 |
| miR-148b, miR-376c, miR-409-3p, miR-801 | 127 BC cases (ER+ [77.1%] vs ER− [15.7%]; LN− [58.2%] vs LN+ [34.6%]; Stage I–II [76.3%] vs Stage III–IV [7.8%]) and 80 healthy controls | Plasma | TaqMan qRT-PCR (Thermo Fisher Scientific) | miRNA changes separate BC cases from controls. | 137 |
| miR-155, miR-205 | 20 BC cases (ER+ [65%] vs ER− [35%]; Stage I–II [65%] vs Stage III [35%]) and ten healthy controls | Plasma | TaqMan qRT-PCR (Thermo Fisher Scientific) | miRNA changes separate BC cases from controls. | 138 |
| miR-182 | 46 BC patients (ER+ [63%] vs ER− [37%]) and 58 healthy controls | Serum | SYBR green qRT-PCR (Qiagen) | Increased circulating levels of miR-182 in BC cases. | 139 |
| miR-484 | Training set: 39 early-stage BC cases (ER+ [71.8%] vs ER− [28.2%]; LN− [48.7%] vs LN+ [51.3%]) and ten healthy controls Validation set: 98 early-stage BC cases (ER+ [44.9%] vs ER− [55.1%]; LN− [44.9%] vs LN+ [55.1%]) and 25 healthy controls |
Serum | TaqMan qRT-PCR (Thermo Fisher Scientific) | Increased circulating levels of miR-484 in BC cases. | 140 |
Notes: This is a representative sample of 20 recent studies found on a PubMed query (breast cancer blood miRNA miR) that describe individual miRNAs or miRNA signatures having potential application for early disease detection. Studies with fewer than 20 BC cases were excluded. While these signatures mainly reflect higher amounts of circulating miRNAs, some miRNAs are detected at lower levels in blood samples of BC patients. Blood collection was performed before surgery unless otherwise indicated. miRNAs shown in bold indicate a recurrent presence in at least three independent studies.
Abbreviations: BC, breast cancer; DCIS, ductal carcinoma in situ; ER, estrogen receptor; LN, lymph node status; miRNA, microRNA; qRT-PCR, quantitative real-time polymerase chain reaction.