Circulating miR-627-5p and miR-199a-5p are promising diagnostic biomarkers of colorectal neoplasia

Table 1 Clinical characteristics of all patients with colorectal cancer, advanced adenoma and healthy controls

Factors		Phase II				Phase III
		CRC (n = 60)	AA (n = 60)	HC (n = 30)	P value	CRC (n = 30)	AA (n = 33)	HC (n = 20)	P value
Age (yr)		66.95 ± 10.52	62.70 ± 10.58	63.60 ± 7.60	0.06	65.40 ± 10.10	60.27 ± 10.07	61.40 ± 8.15	0.10
Gender	Male	41 (68.33%)	42 (70.00%)	20 (66.67%)	0.95	21 (70%)	25 (75.76%)	17 (85.00%)	0.48
	Female	19 (31.67%)	18 (30.00%)	10 (33.33%)		9 (30%)	8 (24.24%)	3 (15.00%)
Lymph node metastasis	Present	21 (35.00%)				9 (30%)
	Absent	39 (65.00%)				21 (70%)
TNM stage	I-II	37 (61.67%)				20 (66.67%)
	III-IV	23 (38.33%)				10 (33.33%)
Histology	SSA	0 (0%)	1 (1.67%)			0 (0%)	1 (3.03%)
	TA	0 (0%)	35 (58.33%)			0 (0%)	18 (54.55%)
	TVA	0 (0%)	24 (40.00%)			0 (0%)	14 (42.42%)
	Adenocarcinoma	60 (100%)				30 (100%)

CRC: Colorectal cancer; AA: Advanced adenoma; HC: Healthy control; SSA: Sessile serrated adenoma; TA: Tubular adenoma; TVA: Tubulovillous adenoma.

Table 2 Diagnostic power of each marker for colorectal cancer and advanced adenoma

		AUC	Sensitivity	Specificity	Cut-off value	P value
CRC vs HC	miR-627-5p	0.97	0.87	1.00	2.21	< 0.001
	miR-199a-5p	0.90	0.93	0.70	1.79	< 0.001
	CEA	0.70	0.32	1.00	7.83	< 0.01
	CA199	0.54	0.12	1.00	42.50	0.52
	Integrated model	0.98	0.87	1.00	0.84	< 0.001
AA vs HC	miR-627-5p	0.84	0.62	0.93	1.87	< 0.001
	miR-199a-5p	0.76	0.90	0.53	1.35	< 0.001
	CEA	0.50	0.80	0.33	1.44	0.95
	CA199	0.43	1.00	0.04	1.31	0.27
	Integrated model	0.86	0.78	0.77	0.59	< 0.001
CRC+AA vs HC	miR-627-5p	0.90	0.77	0.93	1.87	< 0.001
	miR-199a-5p	0.83	0.81	0.70	1.78	< 0.001
	CEA	0.60	0.90	0.30	1.28	0.12
	CA199	0.49	0.07	1.00	42.50	0.80
	Integrated model	0.92	0.83	0.87	0.74	< 0.001

CRC: Colorectal cancer; AA: Advanced adenoma; HC: Healthy control; CA199: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.

Table 3 Correlations between serum miR-627-5p and miR-199a-5p expression levels and clinicopathological features in colorectal cancer patients

Variable		n (%)	miR-627-5p		miR-199a-5p
			Median (IQR)	P value	Median (IQR)	P value
Age (yr)	< 65	24 (40.00)	4.15 (2.43-8.82)	0.23	4.14 (2.36-6.52)	0.38
	≥ 65	36 (60.00)	5.92 (3.36-8.41)		3.86 (2.55-9.87)
Gender	Male	41 (68.33)	6.46 (3.24-7.60)	0.03	7.80 (5.76-10.04)	0.04
	Female	19 (31.67)	4.16 (2.22-6.05)		5.82 (3.89-7.91)
Tumor size	< 4 cm	20 (33.33)	4.30 (2.22-6.05)	0.04	6.15 (3.91-7.79)	0.03
	≥ 4 cm	40 (66.67)	6.12 (3.46-7.59)		7.71 (5.57-9.99)
Lymph node metastasis	Absent	39 (65.00)	5.10 (2.59-7.19)	0.93	5.87 (3.86-8.98)	0.52
	Present	21 (35.00)	5.07 (2.63-8.20)		3.97 (2.26-7.55)
TNM stage	I-II	37 (61.67)	5.10 (2.78-7.22)	0.77	6.75 (3.87-10.04)	0.17
	III-IV	23 (38.33)	5.07 (2.74-8.45)		3.89 (1.91-7.22)
Histological grade	Well/moderately differentiated	49 (81.67)	4.16 (1.92-6.05)	0.33	5.82 (3.97-9.26)	0.36
	Poorly differentiated/mucinous	11 (18.33)	5.07 (2.78-7.16)		3.85 (3.44-5.87)

IQR: Interquartile range.