Circulating microRNA as diagnostic biomarkers for haematological cancers: a systematic review and meta-analysis

Figures & data

Figure 3 Forest plot of specificity.

Figure 4 Forest plot of the negative likelihood ratio (NLR).

Figure 5 Forest plot of the positive likelihood ratio (PRL).

Figure 6 Forest plot of diagnostic odds ratio (DOR).

Figure 1 Flowchart of studies selection.

Figure 2 Forest plot of sensitivity.

Figure 7 Summary ROC curve for the included studies.

Table 1 Characteristics of included studies

First author, year	Ethnicity	Sample Size		patients	miRNA profiled	Specimen	Expression	QUADAS-2
Case Conrol
Elhamamsy et al, 2016	African	65	50	AML	miR-92a miR-143 miR-342	Plasma Plasma Plasma	up up up	6
Yoshizawa et al, 2012	European	62	21	MM	miR-92a	Plasma	down	5
Swellam et al, 2016	African	85	20	AML	miR-100 miR-196a miR-146a	Plasma Plasma Plasma	up up up	6
Sevcikova et al,2013	European	91	30	MM	miR-29a	Serum		7
Qu et al, 2013	Asian	50	50	MM	miR-483-5p	Plasma	up	7
Kubiczkova et al,2014	European	103	30	MM	miR-34a/let-7e	Serum		6
Hao et al, 2013	Asian	47	15	MM	miR-19a miR-92a	Serum Serum	down up	6
Ohyashiki et al,2011	Asian	144	37	NHL	miR-92a/miR-638	Plasma	down	7
Mao et al, 2014	Asian	93	210	PCNSL	miR-21	Serum	up	6
Guo et al, 2010	Asian	79	37	NTCL	miR-221	Plasma	up	6
Fang et al,2012	Asian	75	77	DLBCL	miR-15a miR-16–1 miR-34a miR-155 miR-29c	Serum Serum Serum Serum Serum	up up down up up	7
Xie et al, 2012	Asian	45	30	AML	miR-21 miR-155 miR-210 miR-221	Serum Serum Serum Serum	up up up up	5
Zhi et al, 2013	Asian	140	135	AML	miR-10a-5p miR-93-5p miR-129-5p miR-155-5p miR-181b-5p miR-320d	Serum Serum Serum Serum Serum Serum	up up up up up up	6
Wang et al, 2012	Asian	52	100	AML	miR-29a miR-142-3p miR-29a/miR-142-3p	Plasma Plasma Plasma	down down down	5
Fayyad et al, 2013	European	20	20	AML	miR-150 miR-342 miR-150/miR-342	Plasma Plasma Plasma	down down down	6
Qu X et al, 2014	Asian	40	20	MM	miR-483-5p miR-20a	Plasma Plasma	up down	6
Yu J et al, 2013	Asian	40	30	MM	miR-202	Serum	up	6
Jones CI,2012	European	24	13	MM	miR-720 miR-1308	Serum Serum	up down	6

Abbreviations: MM, Multiple myeloma; AML, Acute myeloid leukaemia, NHL, Non-Hodgkin Lymphoma; DLBCL, Diffuse Large B Cell Lymphoma, PCNSL, primary central nervous system lymphoma, NTCL, NK/T-cell lymphoma.

Table 2 Summary of subgroup analysis for circulating miRNA in haematological cancer diagnosis

Subgroups Overall Ethnicity	Number of studies 50	SEN(95%CI) 0.81 [0.79–0.82]	SPE(95%CI) 0.85 [0.83–0.86]	+LR(95%CI) 5.28 [4.25–6.56]	-LR(95%CI) 0.22 [0.18–027]	DOR(95%CI) 30.39 [21.19–43.61]	AUC(SE) 0.91 [0.02]
Africa	6	0.84 [0.82–0.90]	0.91 [0.87–0.95]	9.37 [4.40–19.95]	0.20 [0.09–0.43]	55.22 [21.23–143.64]	0.95 [0.02]
Asia	36	0.84 [0.80–0.88]	0.84 [0.82–0.85]	4.99 [3.89–6.41]	0.23 [0.19–0.29]	26.61 [17.55–40.36]	0.94 [0.02]
European	8	0.84 [0.80–0.88]	0.84 [0.78–0.89]	4.43 [2.89–6.81]	0.21 [0.15–0.28]	22.98 [12.34–42.77]	0.89 [0.02]
miRNA
Multiple miRNA	5	0.88 [0.85–0.91]	0.94 [0.91–0.97]	11.61 [3.99–33.72]	0.14 [0.08–0.24]	93.15 [21.14–404.67]	0.92 [0.05]
Single miRNA	45	0.79 [0.78–0.81]	0.84 [0.82–0.85]	4.92 [3.95–6.13]	0.24 [0.20–0.29]	25.37[17.76–36.22]	0.90 [0.01]
Sample Types
Plasma	28	0.76 [0.74–0.78]	0.89 [0.87–0.91]	6.29 [4.35–9.10]	0.27 [0.22–0.34]	30.77 [19.08–46.64]	0.87 [0.03]
Serum	22	0.85 [0.83–0.87]	0.81 [0.79–0.83]	4.69 [3.54–6.20]	0.18 [0.14–0.24]	27.56 [16.30–46.61]	0.91 [0.02]
Types of Disease
Lymphoma	8	0.87 [0.84–0.89]	0.76 [0.73–0.80]	3.48 [2.31–5.23]	0.15 [0.07–0.31]	30.66 [11.41–82.44]	0.91 [0.04]
MM	19	0.75 [0.73–0.78]	0.84 [0.81–0.87]	4.55 [3.30–6.27]	0.28 [0.23–0.35]	17.65 [11.00–28.33]	0.86 [0.03]
Leukemia	23	0.89 [0.81–0.84]	0.89 [0.87–0.90]	7.06 [5.08–9.80]	0.19 [0.14–0.27]	48.55 [27.30–86.36]	0.93 [0.02]

Abbreviations: SEN, Sensitivity; SPE, Specificity; +LR, Positive likelihood ratio;-NR, Negative likelihood ratio; DOR, Diagnostic overall ratio; AUC, Area under curve.