Diagnostic accuracy of circulating miR-146, miR-221 and miR-222 in papillary thyroid cancer: A systematic review and meta-analysis

Table 1 Basic characteristics of the included studies

Ref.	Year	Country	Total PTC/BN/HC cases (n)	Male/females (n)	Age	miRNA tested
Lee et al[26]	2014	Korea	70/19/0	15/74	BN: 49.79 ± 12.49, PTC (no nodal involvement) 51.4 ± 12.66, PTC (with nodal involvement) 51.51 ± 15.34	miR-146b, miR-221, miR-222, miR-155
Zhang et al[24]	2017	China	85/35/40	50/110	PTC-49 were < 45 years, 36 were ≥ 45 years. BN: 21 were < 45 years and 19 were ≥ 45 years	miR-146b, miR-221, miR-222, miR-16
Zhang et al[27]	2018	China	58/35/40	NG	PTMC: 26 were < 45 years, 32 were ≥ 45 years. PTC: 31 were < 45 years, 16 were ≥ 45 years	miR-146b, miR-221, miR-222, miR-16, miR-21
Rosignolo et al[23]	2017	Italy	44/19/20	NG	NG	mi-146a-5p, miR-221-3p, miR-222-3p, miR-146b-5p, miR-191-5p, miR-103a-3p, miR-28-3p
Jiang et al[25]	2020	China	64/0/0	14/50	PTC without LNM: 42.2 ± 13. PTC with LNM: 41.0 ± 12.7	miR-21-52, miR-146b-5p, miR-204-5p, miR-221-3p, miR-222-3p, miR-451a, miR-7-5p, miR-30a-3p, miR-138-5p, miR-199a-3p
Yu et al[22]	2012	China/Canada	106/95/44	61/184	PTC: 65 were < 45 years and 41 were ≥ 41 years. BN: 60 were < 45 years and 35 were ≥ 45 years	let-7e, miR-181b, miR-1975, miR-144, miR-100, miR-151-5p, miR-222, miR-543, miR-127-3p, miR-16

PTC: Papillary thyroid cancer; BN: Benign nodule; HC: Healthy controls; PTMC: Thyroid papillary microcarcinoma; LNM: Lymph node metastasis; NG: Not given.

Table 2 Papillary thyroid cancer characteristics among the included studies

Ref.	Lymph node metastasis (n)	Distant metastasis (n)	Extrathyroid extension (n)	Multifocality (n)	PTC recurrence (n)	Tumor size
Lee et al[26]	45	0	40	NG	NG	Benign: 29.48 ± 11.25 mm. PTC (node negative): 10.50 ± 7.67 mm. PTC (node negative): 13.71 ± 8.29 mm
Zhang et al[24]	59	29	17	20	12	PTC (newly diagnosed)-64 were ≤ 2 cm and 21 were > 2 cm
Zhang et al[27]	61	40	18	34	NG	NG
Rosignolo et al[23]	32	3	24	12	NG	Screening cohort median size and range in mm: 11 (5-33). Validation cohort median and range in mm: 10 (1-60)
Yu et al[22]	60	20	NG	36	NG	PTC: 67 were ≤ 2 cm and 39 were > 2 cm
Jiang et al[25]	49	8	NG	20	3	PTC without LNM (mm): 10.6 ± 4.2 of which 2 were > 20 mm and 13 were ≤ 20 mm. PTC with LNM (mm): 13.5 ± 5.5 of which 8 were > 20 mm and 41 were ≤ 20 mm

PTC: Papillary thyroid cancer; LNM: Lymph node metastasis; NG: Not given.

Table 3 Quality assessment of the included studies

Ref.	Risk of bias				Applicability concerns
	Patient selection	Index test	Reference standard	Flow and timing	Patient selection	Index test	Reference standard
Lee et al[26]	Low risk	Unclear risk	Low risk	Low risk	Low risk	Unclear risk	Low risk
Zhang et al[24]	High risk	Unclear risk	Low risk	Low risk	High risk	Unclear risk	Low risk
Zhang et al[27]	High risk	Unclear risk	Low risk	Low risk	High risk	Unclear risk	Low risk
Rosignolo et al[23]	Low risk	Unclear risk	Low risk	Low risk	Low risk	Unclear risk	Low risk
Jiang et al[25]	Low risk	Unclear risk	Low risk	Low risk	Low risk	Unclear risk	Low risk
Yu et al[22]	Low risk	Unclear risk	Low risk	Low risk	Low risk	Unclear risk	Low risk