Blood miRNAs as Potential Diagnostic Biomarkers for Chronic Obstructive Pulmonary Disease: A Meta-Analysis

Figures & data

Table 1 The Basic Characteristics of the Included Studies

First Author	Year	Country	Language	No. of COPD Patients	Age	Sex (Male/Female)	No. of Control	Age	Sex (Male/Female)	Sample Type	Test Method	Normalizer
Chen et al^Citation17	2019	China	English	104	SCOPD: 67.53±8.49, AECOPD: 65.13±9.87	88/16	50	63.47±11.31	41/9	Plasma	qRT-PCR	U6
Ding et al^Citation18	2023	China	English	59	75.12 ± 7.85	50/9	26	71.65 ± 6.35	20/6	Plasma	qRT-PCR	Cel-miR-39-3p
Gao et al^Citation19	2022	China	Chinese	164	SCOPD: 67.97±8.24, AECOPD: 69.12±7.89	107/57	82	68.27±8.22	57 /25	Plasma	qRT-PCR	U6
Geng et al^Citation20	2020	China	English	53	60.32± 6.35	32/21	50	59.83±5.29	25/25	Serum	qRT-PCR	U6
Jiang et al^Citation21	2021	China	Chinese	180	57.84±6.59	104/76	80	58.23±8.34	49/31	Serum	qRT-PCR	U6
Li et al^Citation22	2022	China	Chinese	262	SCOPD: 62.85±12.08, AECOPD: 64.24±11.03	151/111	110	60.78±10.77	60/50	PBMC	qRT-PCR	U6
Li et al^Citation23	2023	China	Chinese	100	SCOPD:56.41 ± 6.22, AECOPD: 57.43 ± 6.11	63/37	50	56.86 ± 6.51	30/20	Serum	qRT-PCR	U6
Shen et al^Citation24	2021	China	English	46	62.3±5.6	36/10	34	61.2±6.3	27/7	Plasma	qRT-PCR	U6
Shi et al^Citation25	2022	China	English	35	66.89±8.05	24/11	35	66.89±5.86	25/10	Plasma	qRT-PCR	U6
Soeda et al^Citation26	2013	Japan	English	40	Ex-smoker: 64.6±7.4, Current smoker: 64.7±7.5	36/4	10	62.8±14.6	10/0	Plasma	qRT-PCR	Ath-miR-159
Wang et al^Citation27	2023	China	English	108	SCOPD:77.1 ± 9.12, AECOPD: 78.4 ± 10.11	88/20	45	75.9 ± 2.66	22/23	Serum	qRT-PCR	U6
Wei et al^Citation28	2022	China	Chinese	43	SCOPD:57.87 ± 11.12, AECOPD: 70.79 ± 8.08	38/5	26	62.27 ± 7.56	15/11	Blood	qRT-PCR	U6
Zeng et al^Citation29	2020	China	Chinese	136	65.30 ±10.80	84/52	60	6 4. 2 0 ± 1 0. 5 0	39/21	Plasma	qRT-PCR	U6
Zhao et al^Citation30	2019	China	Chinese	127	64.05±6.82	78/49	50	NA	NA	PBMC	qRT-PCR	NA
Zhou et al^Citation31	2021	China	Chinese	205	SCOPD: 67.38±3.80, AECOPD: 67.45±7.62	162/43	101	68.22±6.83	78/23	Serum	qRT-PCR	U6
Li et al^Citation32	2020	China	English	103	73 (53–85)	79/24	101	60 (50–80)	84/17	Blood	qRT-PCR	U6

Abbreviations: AECOPD, Acute Exacerbations of Chronic Obstructive Pulmonary Disease; COPD, Chronic Obstructive Pulmonary Disease; NA, not available; qRT-PCR, Quantitative Reverse Transcription Polymerase Chain Reaction.

Figure 1 Flow chart for inclusion and exclusion of literature.

Figure 2 The blood miRNA was utilized to differentiate between COPD patients and the healthy control group in the meta-analysis results. Forest plot of (a) SSEN, (b) SSPE, (c) SPLR, (d) SNLR and (e) DOR. (f) AUC of SROC. (g) The fagan’s nomogram. (h) The results of publication bias.

Figure 3 The blood miRNA was utilized to differentiate between AECOPD patients and the SCOPD patients in the meta-analysis results. Forest plot of (a) SSEN, (b) SSPE, (c) SPLR, (d) SNLR and (e) DOR. (f) AUC of SROC. (g) The fagan’s nomogram. (h) The results of publication bias.

Table 2 Meta Regression and Subgroup Analysis of the Meta-Analysis

	Parameter	Category	No. of Studies	Sensitivity	P value	Specificity	P value
COPD vs Health	Sample>100	Yes	9	0.87 0.80–0.93	0.28	0.77 0.69–0.84	0.02
		No	9	0.78 0.67–0.88		0.76 0.67–0.85
	English	Yes	13	0.86 0.80–0.92	0.66	0.79 0.73–0.85	0.26
		No	5	0.74 0.60–0.89		0.69 0.58–0.81
	U6	Yes	16	0.84 0.78–0.90	0.69	0.75 0.69–0.81	0.03
		No	2	0.70 0.44–0.96		0.92 0.82–1.00
	Plasma	Yes	11	0.82 0.73–0.90	0.03	0.78 0.70–0.85	0.05
		No	7	0.85 0.75–0.94		0.74 0.65–0.84
	Serum	Yes	5	0.89 0.81–0.97	0.42	0.72 0.61–0.83	0.01
		No	13	0.80 0.72–0.88		0.78 0.71–0.84
	Cut-off value	Yes	14	0.86 0.80–0.91	0.93	0.78 0.72–0.84	0.35
		No	4	0.70 0.52–0.87		0.70 0.56–0.84
AECOPD vs SCOPD	English	Yes	2	0.64 0.47–0.81	<0.01	0.82 0.69–0.95	0.26
		No	7	0.88 0.84–0.93		0.80 0.72–0.87
	Plasma	Yes	3	0.86 0.74–0.97	0.30	0.77 0.65–0.89	0.03
		No	6	0.84 0.75–0.93		0.81 0.74–0.89
	Serum	Yes	4	0.83 0.72–0.94	0.10	0.87 0.82–0.92	0.12
		No	5	0.86 0.77–0.95		0.73 0.66–0.79
	Cut-off value	Yes	8	0.84 0.76–0.91	0.26	0.81 0.75–0.88	1
		No	1	0.92 0.80–1.00		0.71 0.48–0.94

Abbreviations: AECOPD, Acute Exacerbations of Chronic Obstructive Pulmonary Disease; COPD, Chronic Obstructive Pulmonary Disease.

Figure 4 (a) The results of univariable meta-regression and subgroup analyses.(a) The blood miRNA was utilized to differentiate between COPD patients and the healthy control group in the meta-analysis results. (b) The blood miRNA was utilized to differentiate between AECOPD patients and the SCOPD patients in the meta-analysis results.

Figure 5 The sensitivity analysis was conducted using blood miRNA to distinguish between COPD patients and the healthy control group. (a) goodness-of-fit, (b) bivariate normality, (c) influence analysis, and (d) outlier detection.

Figure 6 The sensitivity analysis was conducted using blood miRNA to distinguish between AECOPD patients and the SCOPD patients. (a) goodness-of-fit, (b) bivariate normality, (c) influence analysis, and (d) outlier detection.

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