Identification of Urinary Exosomal miRNAs for the Non-Invasive Diagnosis of Prostate Cancer

Figures & data

Table 1 Expression of seven Significantly Deregulated miRNAs Between Localized PCa Patients and Metastatic PCa Patients Determined by NGS Technology

miRNAs	Expression Level		Up/Down	|log2(FC)|
	Localized PCa	Metastatic PCa
hsa-miR-16-2-3p	22.45	0.00	Down	3.67
hsa-miR-375	67.18	5.28	Down	17.78
hsa-miR-451a	2039.60	70.16	Down	4.86
hsa-miR-486-3p	1288.70	27.18	Down	5.92
hsa-miR-486-5p	4096.00	67.68	Down	5.57
hsa-miR-3182	20.00	1.18	Down	4.09
hsa-miR-3615	18.33	0.00	Down	17.48

Table 2 Expression of Significantly Deregulated miRNAs Between PCa Patients and Healthy Controls Determined by NGS Technology

miRNAs	Expression Level		Up/Down	|log2(FC)|
	Healthy Control	PCa
hsa-miR-16-2-3p	0.71	11.23	Up	3.99
hsa-miR-451a	128.51	1054.92	Up	3.04
hsa-miR-486-3p	27.74	657.95	Up	4.57
hsa-miR-486-5p	67.21	2081.85	Up	4.95
hsa-miR-126-5p	0.00	4.24	Up	15.37
hsa-miR-1273g-3p	7.74	43.44	Up	2.49
hsa-miR-199a-5p	3.00	19.02	Up	2.66
hsa-miR-20a-5p	5.24	26.20	Up	2.32
hsa-miR-3656	0.60	8.34	Up	3.80
hsa-miR-4492	5.39	38.21	Up	2.82
hsa-miR-4497	123.01	1018.97	Up	3.05
hsa-miR-4508	5.65	29.17	Up	2.37
hsa-miR-4532	8.54	43.11	Up	2.34
hsa-miR-9-5p	20.11	84.12	Up	2.06
hsa-miR-375	839.54	36.23	Down	4.53
hsa-let-7c-5p	103.31	6.90	Down	3.90
hsa-miR-100-5p	2703.51	215.12	Down	3.65
hsa-miR-10a-5p	3603.55	136.07	Down	4.73
hsa-miR-10b-3p	9.33	0.00	Down	16.51
hsa-miR-10b-5p	1263.99	25.27	Down	5.64
hsa-miR-125a-5p	143.39	18.04	Down	2.99
hsa-miR-125b-5p	227.43	27.48	Down	3.05
hsa-miR-148a-3p	1995.73	261.68	Down	2.93
hsa-miR-149-5p	15.13	1.08	Down	3.80
hsa-miR-151a-3p	589.58	42.22	Down	3.80
hsa-miR-152-3p	78.38	4.43	Down	4.15
hsa-miR-192-5p	1001.74	74.54	Down	3.75
hsa-miR-196a-5p	16.69	1.05	Down	3.99
hsa-miR-200a-5p	39.50	1.39	Down	4.83
hsa-miR-200b-3p	381.33	22.83	Down	4.06
hsa-miR-200b-5p	11.82	0.23	Down	5.70
hsa-miR-200c-3p	348.95	21.77	Down	4.00
hsa-miR-203a-3p	139.19	8.39	Down	4.05
hsa-miR-204-5p	289.56	19.36	Down	3.90
hsa-miR-205-5p	85.99	14.43	Down	2.58
hsa-miR-23b-3p	30.03	3.50	Down	3.10
hsa-miR-27b-3p	103.87	15.73	Down	2.72
hsa-miR-28-3p	145.02	12.22	Down	3.57
hsa-miR-30a-3p	276.16	12.15	Down	4.51
hsa-miR-30a-5p	3273.13	104.62	Down	4.97
hsa-miR-30b-5p	19.22	2.37	Down	3.02
hsa-miR-30c-5p	160.87	17.00	Down	3.24
hsa-miR-30d-5p	920.00	114.22	Down	3.01
hsa-miR-30e-3p	9.54	0.85	Down	3.49
hsa-miR-361-3p	108.73	12.48	Down	3.12
hsa-miR-365a-5p	3.86	0.00	Down	15.24
hsa-miR-429	13.27	1.40	Down	3.25
hsa-miR-509-3p	7.40	0.00	Down	16.18
hsa-miR-514a-3p	21.39	0.76	Down	4.82
hsa-miR-532-5p	294.17	24.93	Down	3.56
hsa-miR-664a-5p	12.81	0.88	Down	3.86
hsa-miR-99b-3p	21.03	0.84	Down	4.65
hsa-miR-99b-5p	490.76	30.43	Down	4.01

Figure 1 Expression of 5 candidate exosomal miRNAs in the urine samples of the validation cohort. Relative expression levels of urinary exosomal miR-375 (A), miR-16-2-3p (B), miR-486-3p (C), miR-451a (D), and miR-486-5p (E) in patients with PCa. Data presented as relative fold changes.

Figure 2 Receiver operator characteristic curve (ROC) for 4 individual miRNAs (miR-375, miR-451a, miR-486-3p and miR-486-5p) and their combination to differentiate between PCa patients and healthy controls.

Table 3 Clinical Characteristics of Participants in the qRT-PCR Cohort

Characteristics	PCa Patients	BPH Patients	Healthy Controls
Total number	47	29	25
Age(years), median (IQR)	69.00 (65.00–72.00)	68.50 (61.25–72.00)	68.50 (61.25–71.00)
PSA(ng/mL),median (IQR)	16.91 (7.42–48.76)	2.77 (1.35–6.97)	0.93 (0.64–1.68)
Gleason score
≤6	6
7	19
≥8	22
Clinical stage
≤T2	26
>T2	21
Metastasis
No	32
Yes	15

Figure 3 Expression of urinary exosomal miRNAs in PCa patients and BPH patients. Relative expression levels of urinary exosomal miR-375 (A), miR-451a (B), miR-486-3p (C), and miR-486-5p (D). Data are presented as relative fold changes.

Figure 4 Evaluation of the ability of the miRNA-based panel and PSA to differentiate between patients with PCa and patients with BPH. Receiver operator characteristic (ROC) curve for PSA, two individual miRNAs (miR-375 and miR-451a) and their combination to differentiate between two groups consisting of 47 PCa patients and 29 BPH patients.

Figure 5 Expression of urinary exosomal miRNAs in localized PCa and metastatic PCa. Relative expression levels of urinary exosomal miR-375 (A), miR-451a (B), miR-486-3p (C), and miR-486-5p (D) in localized PCa patients and metastatic PCa patients. Data presented as relative fold changes.

Figure 6 Receiver-operating characteristic curve (ROC) for urinary exosomal miR-375 and PSA to differentiate between localized PCa patients and metastatic PCa patients.