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Table 2 Cell-free miRNA in DLBCL

From: Circulating RNA biomarkers in diffuse large B-cell lymphoma: a systematic review

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

  1. 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