Table 2.
Cell-free miRNA in DLBCL
| References | Method | Sample | miRNA | Level | Result |
|---|---|---|---|---|---|
| Diagnosis | |||||
| Lawrie et al. [53] | RT-qPCR serum |
60 DLBCL 43 controls |
miR-21, miR-155, miR-210 | Up | Higher level in DLBCL |
| Fang et al. [55] | RT-qPCR serum |
75 DLBCL 77 controls |
miR-15a, miR-16-1, miR-29c, miR-155 miR-34a miR-21, miR-223 |
Up Down NS |
Higher level in DLBCL Lower level in DLBCL No difference |
| Chen et al. [59] | RT-qPCR serum |
62 DLBCL 50 controls |
miR-21 | Up | Higher level in DLBCL, especially in lower stage disease |
| Inada et al. [64] | RT-qPCR (exosome-enriched) serum |
33 DLBCL 22 controls |
miR-15a-3p, miR-21-5p, miR-210-5p miR-181a-5p miR-155-5p, miR-210-3p |
Up Down NS |
Higher level in DLBCL Lower level in DLBCL No difference |
| Li et al. [57] | RT-qPCR serum |
112 DLBCL 45 controls |
miR-21 | Up | Higher level in DLBCL |
| Borges et al. [ 56] | RT-qPCR serum |
21 DLBCL 6 controls |
miR-17, miR-20b, miR-210, miR-296 | NS | No difference |
| Yuan et al. [58] | RT-qPCR serum |
56 DLBCL 20 controls |
miR-21, miR-125b, miR-130a, miR-155, miR-200c miR-29c, miR-145, miR-451 |
Up Down |
Higher level in DLBCL Lower level in DLBCL |
| Khare et al.[63] | RNA seq (exosome-enriched) plasma |
14 DLBCL 20 controls |
miR-124, miR-532-5p miR-122, miR-128, miR-141, miR-145, miR-197, miR-345, miR-424, miR-425, miR-101, let-7e, miR-222, miR-29c, miR-375, miR-324-5p, miR-135a, miR-379, let-7 i, miR-32 |
Up Down |
Higher level in DLBCL Lower level in DLBCL |
| Bedewey et al. [79] | RT-qPCR serum |
54 DLBCL 15 controls |
miR-155 | Up | Higher level in DLBCL |
| Zheng et al.[61] | RT-qPCR serum |
203 DLBCL 100 controls |
miR-21 | Up | Higher level in DLBCL |
| Ahmadvand et al. [78] | RT-qPCR plasma |
40 DLBCL 38 controls |
miR-155 | Up | Higher level in DLBCL |
| Meng et al.[62] | RNA seq/RT-qPCR serum |
3 DLBCL 3 controls |
miR-34a-5p miR-323b-3p, miR-431-5p 2588 miRNAs (51 different expressed miR) |
Up Down |
Higher level in DLBCL Lower level in DLBCL |
| Cui et al. [65] | RT-qPCR plasma |
22 DLBCL 14 controls |
miR-494, miR-21 mir-155 |
Up NS |
Higher level in DLBCL No difference |
| Marchesi et al. [171] | Microarray/RT-qPCR serum |
36 DLBCL 36 controls |
miR-22, miR-18a, miR-20a, let-7c, miR-99a, miR-125b | NS | No difference |
| Zheng et al.[60] | RT-qPCR serum |
200 DLBCL 100 controls |
miR-155 | Up | Higher level in DLBCL |
| Beheshti et al. [69] | ddPCR serum |
86 DLBCL 17 controls |
miR-15a, miR-18a, miR-24, let-7b, let-7c miR-10b, miR-27a, miR-130a, miR-155 |
Up NS |
5-miRNA signature (higher level of let-7b, let-7c, miR-18a, miR-24, and miR-15a) was associated with DLBLC |
| Jorgensen et al. [66] | RT-qPCR plasma |
38 DLBCL 41 controls |
miR-199a-5p, miR-326, miR-328, miR-21-5p miR-375 miR 155-5p, miR-19a-3p, miR-19b-3p, miR-92a-3p, miR-10b-5p, miR-210, miR-363-3p |
Up Down NS |
Higher level in DLBCL Lower level in DLBCL Higher level of miR-199a-5p and miR-326, and lower level of miR-375 may predict future B-cell lymphoma development |
| Subtype classification | |||||
| Chen et al. [59] | RT-qPCR serum |
62 DLBCL 50 controls |
miR-21 | Up | Higher level in ABC subtype compared to GCB subtype |
| Song et al. [81] | RT-qPCR serum | 173 DLBCL | miR-33a, miR-224, miR-455-3p, miR-520d-3p, miR-1236 | NS | No difference between ABC and GCB subtype |
| Bedewey et al. [79] | RT-qPCR serum |
54 DLBCL 15 controls |
miR-155 | Up | Higher level in non-GCB compared to GCB subtype |
| Response to therapy (R-CHOP) | |||||
| Song et al. [81] | RT-qPCR serum | 133 DLBCL |
miR-224, miR-520d-3p, miR-1236 miR-33a, miR-455-3p Others (731 miRNA), including miR-21 |
Up Down NS |
5-miRNA signature (higher level of miR-224, miR-520d-3p, miR-1236; lower level of miR-33a, miR-455-3p) was associated with superior response to therapy |
| Yuan et al. [58] | RT-qPCR serum |
56 DLBCL 20 controls |
miR-125b, miR-130a miR-21, miR-29c, miR-145, miR-155, miR-200c, miR-451 |
Up NS |
Higher level was associated with inferior response. no association with response to therapy |
| Bouvy et al. [80] | Microarray/RT-qPCR plasma |
19 DLBCL 1 control |
miR-21, miR-197, miR-19b, miR-20a, miR-451 miR-122, let-7e |
Up NS |
Higher level of miR-21 and miR-197 during treatment was associated with inferior response. higher level of miR-19b, miR-20a, and miR-451 after 4 cycles R-CHOP differentiates patient group with CR from patient group with residual tumor |
| Cui et al. [65] | RT-qPCR plasma | 56 DLBCL | miR-494, miR-21 | Down | Higher pretreatment level of miR-494 was associated with interim-PET/CT negativity. Lower posttreatment miR-494 and miR-21 level compared to pretreatment values was associated with interim-PET/CT negativity |
| Marchesi et al. [171] | Microarray/RT-qPCR serum |
36 DLBCL 36 controls |
miR-22, let-7c, miR-125b, miR-99a | NS | No association with response to therapy |
| Fajardo-Ramirez et al. [82] | Microarray plasma | 16 DLBCL |
miR-105-5p, miR-186-5p, miR-19a-3p, miR-572, miR-1267, miR-555, miR-205-5p, miR-490-5p, miR-520d-3p miR-100-5p, miR-1910-5p, miR-24-3p, miR-628-3p, miR-766-3p, miR-615-3p |
Up Down |
15-miRNA signature differentiates patients with non-response from patients with CR |
| Prognosis | |||||
| Lawrie et al. [53] | RT-qPCR serum | 52 DLBCL |
miR-21 miR-155, miR-210 |
Up NS |
Higher level was associated with favorable RFS No association with prognosis |
| Chen et al. [59] | RT-qPCR serum |
62 DLBCL 50 controls |
miR-21 | Up | Higher level was associated with favorable RFS |
| Song et al. [81] | RT-qPCR serum | 133 DLBCL |
miR-224, miR-520d-3p, miR-1236 miR-33a, miR-455-3p 731 other miRNAs, including miR-21 |
Up Down NS |
Higher level of miR-224, miR-520d-3p, miR-1236 and lower level of miR-33a, miR-455-3p was associated with lower MRT and higher probability of remission, independent of IPI score |
| Li et al. [57] | RT-qPCR serum |
112 DLBCL 45 controls |
miR-21 | Up | Higher level was associated with inferior OS, independent of IPI score |
| Borges et al. [56] | RT-qPCR serum |
21 DLBCL 6 controls |
miR-17, miR-20b, miR-210, miR-296 | NS | No difference in relapsed patients |
| Yuan et al. [58] | RT-qPCR serum |
56 DLBCL 20 controls |
miR-125b miR-130a |
Up NS |
Higher level was associated with inferior OS, independent of IPI score No significant association with OS |
| Bedewey et al. [79] | RT-qPCR serum |
54 DLBCL 15 controls |
miR-155 | Up | Higher level was associated with inferior EFS |
| Marchesi et al. [171] | Microarray/RT-qPCR serum |
36 DLBCL 36 controls |
miR-22 miR-18a, miR-20a, let-7c, miR-99a, miR-125b |
Up NS |
Higher level was associated with inferior PFS after R-CHOP, independent of IPI score |
| Ahmadvand et al. [78] | RT-qPCR plasma |
40 DLBCL 38 controls |
miR-155 | Up | Higher level was associated with inferior OS |
| Bouvy et al. [80] | Microarray/RT-qPCR plasma |
19 DLBCL 1 control |
miR-21, miR-197, miR-19b, miR-20a, miR-451 | NS | No association with prognosis |
| Zheng et al.[60] | RT-qPCR serum |
200 DLBCL 100 controls |
miR-155 | Up | Higher level was associated with inferior PFS following R-CHOP, independent of IPI |
| Sun et al. [84] | Microarray/RT-qPCR serum | 120 DLBCL |
miR-21, miR-130b, miR-155 miR-28 |
Up Down |
4-miRNA signature (higher level of miR-21, miR-130b, miR-155; lower level of miR-28) was associated with relapse, as well as inferior PFS and OS after R-CHOP, independent of IPI score |
ABC activated B-cell-like, CR complete response, DFS disease free survival, ddPCR droplet digital PCR, DLBCL diffuse large B-cell lymphoma, EFS event-free survival, GCB germinal center B-cell-like, IPI international prognostic index, miR/miRNA microRNA, MRT median remission time, NR no response, NS not significant, OS overall survival, PFS progression-free survival, PR partial response, RFS relapse-free survival, RT-qPCR reverse-transcription quantitative polymerase chain reaction