MicroRNAs in colorectal cancer: A comparative analysis of circulating and tissue microRNA levels

Table 1 Sociodemographic, and clinical characteristics of the enrolled cohort, mean ± SD (minimum-maximum)

Features	Total (n = 19)
Age	67.58 ± 9.43 (51-83)
Sex (%, female; male)	52.6; 47.4
Localization	Ascending colon (n = 5); transverse colon (n = 2); descending colon (n = 1); sigmoid colon (n = 4); rectosigmoid junction (n = 4); rectum (n = 3)
Grading (%, G1; G2; G3)	G1 15.8; G2 52.6; G3 31.6
TNM classification	T2 N0 M0 (n = 2); T3 N0 M0 (n = 7); T3 N1 M0 (n = 7); T4A N1 M0 (n = 1); T4B N0 M0 (n = 1); T4B N1 M0 (n = 1)
Microsatellite instability (%, yes; no)	10.5; 89.5
BRAF mutation (%, yes; no)	5.3; 94.7
KRAS mutation (%, yes; no)	36.8; 63.2
Lymphovascular invasion (%, yes; no)	42.1; 57.9
Perineural invasion (%, yes; no)	26.3; 73.7
Hemoglobin (g/dL)	11.77 ± 2.84 (7.10-17.50)
White blood cells (× 103/μL)	7616.84 ± 2749.57 (4880.00-14840.00)
Platelets (× 103/μL)	287.79 ± 138.51 (152.00-777.00)
International normalized ratio	1.04 ± 0.08 (0.87-1.22)
Fibrinogen (mg/dL)	435.42 ± 129.52 (275.10-796.00)
Albumin (g/dL)	3.98 ± 0.69 (2.40-5.48)
Cholesterol (mg/dL)	161.46 ± 39.95 (73.00-227.00); available for 18 patients
Triglycerides (mg/dL)	94.19 ± 24.84 (36.00-134.00); available for 17 patients
Alanine aminotransferase (U/L)	23.86 ± 26.38 (5.62-120.00); available for 17 patients
Aspartate transaminase (U/L)	22.16 ± 11.53 (13.00-65.00); available for 18 patients
Urea (mmol/L)	36.01 ± 13.40 (15.00-59.50); available for 18 patients
Creatinine (μmol/L)	0.96 ± 0.22 (0.55-1.33); available for 18 patients
Uric acid (μmol/L)	4.91 ± 1.77 (2.30-8.91); available for 18 patients
Carcinoembryonic antigen (ng/mL)	41.18 ± 112.53 (0.65-444.00); available for 15 patients
Cancer antigen 19-9 (U/mL)	29.22 ± 50.82 (3.47-211.00); available for 16 patients
Alpha-fetoprotein (ng/mL)	3.62 ± 2.88 (1.07-9.40); available for 9 patients

TNM: Tumor-nodes-metastasis.

Table 2 MicroRNAs differentially expressed in tissue and plasma, mean ± SD

MicroRNA	2-∆Ct		FC	P value2	2-∆Ct		FC	P value3
	T	PT			CRC_plasma	CTRL_plasma
miR-26b-5p1	0.372 ± 0.29	0.636 ± 0.39	0.58	< 0.001	0.663 ± 0.33	0.901 ± 0.25	0.73	0.007
miR-101-3p1	1.125 ± 0.80	0.203 ± 0.13	0.61	0.01	1.177 ± 0.81	2.730 ± 0.90	0.64	0.001
miR-30d-5p1	0.270 ± 0.17	0.430 ± 0.32	0.63	0.007	1.677 ± 0.75	2.825 ± 1.02	0.59	< 0.001
miR-1071	0.505 ± 0.25	0.720 ± 0.41	0.70	0.014	1.195 ± 0.50	1.915 ± 1.10	0.62	0.011
miR-21-5p1	15.493 ± 8.49	8.140 ± 6.32	1.90	0.02	10.077 ± 19.87	4.185 ± 1.31	2.40	0.025
miR-145-5p	2.193 ± 1.95	26.580 ± 33.48	0.08	0.001	1.238 ± 0.825	0.350 ± 0.30	3.53	< 0.001
miR-143-3p	1.740 ± 1.69	10.532 ± 12.02	0.16	0.001	0.491 ± 0.35	0.888 ± 0.04	5.52	< 0.001
miR-125b-5p	0.650 ± 0.63	3.295 ± 3.46	0.19	0.001	1.078 ± 1.43	0.392 ± 0.23	2.74	0.002
let-7e-5p	0.240 ± 1.64	0.488 ± 0.46	0.49	0.02	0.118 ± 0.06	0.070 ± 0.28	1.69	0.009
let-7f-5p	0.395 ± 0.25	0.757 ± 0.44	0.52	0.002	0.132 ± 0.08	0.490 ± 0.02	2.71	< 0.001
miR-215-5p	1.690 ± 1.16	3.038 ± 3.00	0.55	0.036	1.122 ± 2.22	0.309 ± 0.11	3.62	0.006
miR-23b-3p	1.367 ± 0.98	2.414 ± 2.06	0.56	0.02	1.501 ± 1.17	0.760 ± 0.40	1.97	0.002
let-7c-5p	1.123 ± 1.73	1.792 ± 1.26	0.62	0.005	0.513 ± 0.21	0.270 ± 0.13	1.89	< 0.001
miR-18a-5p	0.708 ± 0.06	2.193 ± 1.95	2.65	0.049	0.340 ± 0.19	0.473 ± 0.13	0.71	0.009
miR-103a-3p	0.705 ± 0.40	1.025 ± 0.90	0.68	0.022	1.656 ± 0.87	2.730 ± 1.95	0.60	NS
miR-99a-5p	0.462 ± 0.47	0.284 ± 0.41	0.16	0.001	0.169 ± 0.17	0.135 ± 0.09	1.39	NS
miR-10b-5p	0.173 ± 0.11	0.601 ± 0.53	0.28	0.001	0.167 ± 0.08	0.141 ± 0.08	1.24	NS
miR-150-5p	0.308 ± 0.40	0.804 ± 0.90	0.38	0.001	2.715 ± 1.69	5.380 ± 8.72	0.56	NS
miR-26a-5p	1.340 ± 1.03	3.363 ± 2.57	0.39	0.001	0.647 ± 0.36	0.573 ± 0.40	1.16	NS
miR-30c-5p	0.227 ± 0.17	0.563 ± 0.40	0.40	0.001	0.500 ± 0.23	0.527 ± 0.21	0.95	NS
miR-130a-3p	0.036 ± 0.03	0.086 ± 0.07	0.41	0.004	0.496 ± 0.24	0.501 ± 0.24	0.92	NS
let-7a-5p	2.222 ± 1.69	5.198 ± 3.62	0.42	0.002	1.272 ± 0.53	1.140 ± 0.60	1.19	NS
let-7b-5p	1.078 ± 0.94	2.413 ± 1.82	0.44	0.004	7.238 ± 3.71	7.003 ± 1.50	1.03	NS
miR-126-3p	0.866 ± 0.80	1.747 ± 1.47	0.49	0.003	3.996 ± 2.55	3.193 ± 1.02	1.37	NS
miR-30b-5p	0.346 ± 0.17	0.650 ± 0.45	0.53	0.001	0.491 ± 0.24	0.536 ± 0.50	0.88	NS
let-7 g-5p	0.616 ± 0.57	1.078 ± 0.76	0.57	0.003	1.602 ± 0.55	1.995 ± 1.09	0.78	NS
miR-27b-3p	0.060 ± 0.61	1.780 ± 1.18	0.59	0.005	0.841 ± 0.76	0.461 ± 0.18	1.88	NS
miR-22-3p	0.168 ± 0.09	0.230 ± 0.15	0.73	0.014	2.028 ± 0.81	2.757 ± 1.14	0.74	NS
miR-29c-3p	0.800 ± 0.34	0.970 ± 0.64	0.82	0.04	0.914 ± 0.39	0.867 ± 0.38	1.02	NS
miR-16-5p	2.246 ± 2.64	2.561 ± 1.69	0.87	0.024	132.038 ± 56.12	164.355 ± 57.78	0.78	NS

¹The five microRNAs differentially modified both in tissue and plasma show the same trend in term of fold change.

²Tissue, paired analysis (19 tumoral tissue vs 19 peritumoral tissue).

³Plasma case-control (19 colorectal cancer plasma vs 16 control plasma).

T: Tumoral; PT: Peritumoral; CTRL: Control; CRC: Colorectal cancer; FC: Fold change; NS: Not significant.

Table 3 MicroRNAs differentially expressed in tissue and plasma with an opposite trend

MicroRNA	Tissue paired (19 T_tissue vs 19 PT_tissue)	Plasma case-control (19 CRC_plasma vs 16 CTRL_plasma)
miR-145-5p	Decrease, FC = 0.08, P = 0.001	Increase, FC = 3.53, P < 0.001
miR-143-3p	Decrease, FC = 0.16, P = 0.001	Increase, FC = 5.52, P < 0.001
miR-125b-5p	Decrease, FC = 0.19, P = 0.001	Increase, FC = 2.74, P = 0.002
let-7e-5p	Decrease, FC = 0.49, P = 0.02	Increase, FC = 1.69, P = 0.009
let-7f-5p	Decrease, FC = 0.52, P = 0.002	Increase, FC = 2.71, P < 0.001
miR-215-5p	Decrease, FC = 0.55, P = 0.036	Increase, FC = 3.62, P = 0.006
miR-23b-3p	Decrease, FC = 0.56, P = 0.02	Increase, FC = 1.97, P = 0.002
let-7c-5p	Decrease, FC = 0.62, P = 0.005	Increase, FC = 1.89, P < 0.001
miR-18a-5p	Increase, FC = 2.65, P = 0.049	Decrease, FC = 0.71, P = 0.009

T: Tumoral; PT: Peritumoral; CTRL: Control; CRC: Colorectal cancer; FC: Fold change.