The Circulating miRNA Profile of Chronic Hepatitis D and B Patients Is Comparable but Differs from That of Individuals with HBeAg-Negative HBV Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Assays
2.3. Isolation of Circulating HBsAg Particles
2.4. miRNA NGS Reads Bioinformatical Analysis
2.5. Read Mapping and Quantification of Gene Expression
2.6. MiR-B-Index
3. Results
3.1. NGS and Quality Controls
3.2. miRNA Profiling of HBsAg Particles
3.3. miRNA Profiling of Whole Serum
3.4. Differential miRNA Expression among Chronic Hepatitis D and B Patients and Individuals with HBeAg Negative Infection
3.5. MiR-B-Index
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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ENI (25) | CHB (25) | CHD (25) | p | ||
---|---|---|---|---|---|
Age | years | 49.4 (28.5/70.1) | 44.8 (31.8/70.6) | 38.0 (17.9/60.4) | ENI vs. CHB: p = 0.184 ENI vs. CHD: p < 0.003 CHB vs. CHD: p = 0.017 Overall: p = 0.004 |
Gender | F M | 13 (52.0) 12 (48.0) | 12 (48.0) 13 (52.0) | 13 (52.0) 12 (48.0) | ENI vs. CHB: p = 1.000 ENI vs. CHD: p = 1.000 CHB vs. CHD: p = 1.000 Overall: p = 0.948 |
Nationality | Italian Non-Italian | 20 (80) 5 (20) | 21 (84) 4 (16) | 5 (20) 20 (80) | ENI vs. CHB: p = 1.000 ENI vs. CHD: p < 0.001 CHB vs. CHD: p < 0.001 Overall: p < 0.001 |
ALT (U/L) | Median (range) | 21 (9/33) | 110 (40/695) | 65 (19/176) | ENI vs. CHB: p < 0.001 ENI vs. CHD: p < 0.001 CHB vs. CHD: p = 0.001 Overall: p < 0.001 |
HBV Genotype | D Non-D unknown | 25 (100) / / | 25 (100) / / | 10 (83.3) 2 (16.7) 13 | ENI vs. CHB: / ENI vs. CHD: p = 0.035 CHB vs. CHD: p = 0.035 Overall: p = 0.012 |
HBsAg | Log IU/mL | 2.71 (1.75/3.10) | 3.75 (3.05/4.22) | 3.89 (3.09/4.59) | ENI vs. CHB: p < 0.001 ENI vs. CHD: p < 0.001 CHB vs. CHD: p = 0.273 Overall: p < 0.001 |
HBV DNA | Log IU/mL | 2.27 (0.70/3.26) | 6.23 (4.61/8.04) | 1.0 (0.70/7.61) | ENI vs. CHB: p < 0.001 ENI vs. CHD: p < 0.001 CHB vs. CHD: p < 0.001 Overall: p < 0.001 |
Assay | Max Groupmean | Log2 Foldchange | Foldchange | p-Value | FDR p-Value | Bonferroni |
---|---|---|---|---|---|---|
hsa-miR-34a-5p | 52.00 | −3.54 | −11.66 | 1.6 × 10−30 | 8.5 × 10−28 | 2.0 × 10−27 |
hsa-miR-885-3p | 43.84 | −3.76 | −13.59 | 2.9 × 10−30 | 8.5 × 10−28 | 3.7 × 10−27 |
hsa-miR-192-5p | 1121.40 | −2.69 | −6.44 | 8.2 × 10−30 | 1.6 × 10−20 | 1.0 × 10−19 |
hsa-miR-148-3p | 1441.72 | −1.78 | −3.44 | 3.0 × 10−21 | 4.1 × 10−19 | 3.7 × 10−18 |
hsa-miR-27b-3p | 227.80 | −1.81 | −3.51 | 3.5 × 10−21 | 4.1 × 10−19 | 4.5 × 10−18 |
hsa-miR-193b-5p | 32.44 | −2.88 | −7.35 | 1.5 × 10−20 | 1.3 × 10−18 | 1.9 × 10−17 |
hsa-miR-194-5p | 408.28 | −2.30 | −4.94 | 1.6 × 10−20 | 1.3 × 10−18 | 2.0 × 10−17 |
hsa-miR-885-5p | 42.12 | −2.70 | −6.48 | 8.3 × 10−19 | 5.4 × 10−17 | 1.0 × 10−15 |
hsa-miR-100-5p | 64.68 | −2.48 | −5.57 | 8.4 × 10−19 | 5.4 × 10−17 | 1.1 × 10−15 |
hsa-miR-30a-3p | 30.60 | −2.57 | −5.94 | 2.3 × 10−18 | 1.3 × 10−16 | 2.9 × 10−15 |
hsa-miR-146b-5p | 123.68 | −2.30 | −4.92 | 3.3 × 10−18 | 1.8 × 10−16 | 4.2 × 10−15 |
hsa-miR-122-5p | 90,951.56 | −2.51 | −5.71 | 3.7 × 10−18 | 1.8 × 10−16 | 4.6 × 10−15 |
hsa-miR-30a-5p | 257.48 | −1.68 | −3.20 | 7.8 × 10−18 | 3.5 × 10−16 | 9.8 × 10−15 |
hsa-miR-483-3p | 173.36 | −2.55 | −5.87 | 4.8 × 10−17 | 2.0 × 10−15 | 6.0 × 10−14 |
hsa-miR-125b-5p | 1516.76 | −1.99 | −3.97 | 4.6 × 10−16 | 1.8 × 10−14 | 5.8 × 10−13 |
hsa-miR-23b-3p | 130.60 | −2.01 | −4.02 | 1.3 × 10−14 | 4.8 × 10−13 | 1.7 × 10−11 |
hsa-miR-146b-3p | 10.36 | −2.79 | −6.93 | 3.0 × 10−14 | 1.0 × 10−12 | 3.7 × 10−11 |
hsa-miR-378a-3p | 84.44 | −1.48 | −2.78 | 1.0 × 10−13 | 3.4 × 10−12 | 1.3 × 10−10 |
hsa-let-7c-5p | 778.48 | −2.12 | −4.36 | 2.4 × 10−13 | 7.2 × 10−12 | 3.0 × 10−10 |
hsa-miR-193a-5p | 117.48 | −1.36 | −2.56 | 2.6 × 10−13 | 7.4 × 10−12 | 3.2 × 10−10 |
hsa-miR-194-3p | 4.84 | −4.00 | −16.02 | 5.7 × 10−13 | 1.6 × 10−11 | 7.2 × 10−10 |
hsa-miR-125b-2-3p | 4.64 | −3.52 | −11.49 | 6.0 × 10−13 | 1.6 × 10−11 | 7.6 × 10−10 |
hsa-miR-200a-3p | 14.20 | −2.82 | −7.05 | 1.2 × 10−12 | 3.1 × 10−11 | 1.6 × 10−9 |
hsa-miR-99a-5p | 89.64 | −1.87 | −3.65 | 1.4 × 10−12 | 3.3 × 10−11 | 1.7 × 10−9 |
hsa-miR-122-3p | 26.60 | −2.67 | −6.39 | 1.7 × 10−12 | 3.9 × 10−11 | 2.1 × 10−9 |
hsa-miR-30c-5p | 65.96 | −1.26 | −2.40 | 5.6 × 10−12 | 1.3 × 10−10 | 7.1 × 10−9 |
hsa-miR-200b-3p | 7.40 | −2.88 | −7.37 | 1.3 × 10−11 | 2.8 × 10−10 | 1.6 × 10−8 |
hsa-miR-365a-3p | 10.24 | −2.27 | −4.84 | 1.6 × 10−11 | 3.4 × 10−10 | 2.1 × 10−8 |
hsa-miR-455-3p | 6.60 | −2.97 | −7.84 | 2.7 × 10−11 | 5.4 × 10−10 | 3.4 × 10−8 |
hsa-miR-574-3p | 65.44 | −1.74 | −3.35 | 4.0 × 10−11 | 7.7 × 10−10 | 5.0 × 10−8 |
hsa-miR-378a-5p | 4.76 | −2.08 | −4.23 | 1.2 × 10−8 | 2.2 × 10−7 | 1.5 × 10−6 |
hsa-miR-223-3p | 3152.68 | 1.63 | 3.09 | 1.3 × 10−8 | 2.3 × 10−7 | 1.6 × 10−5 |
hsa-miR-455-3p | 2.84 | −2.75 | −6.73 | 2.4 × 10−8 | 4.2 × 10−7 | 3.0 × 10−5 |
hsa-miR-203a-3p | 10.84 | −1.85 | −3.59 | 3.4 × 10−8 | 5.8 × 10−7 | 4.3 × 10−5 |
hsa-miR-142-5p | 156.32 | 1.29 | 2.45 | 4.8 × 10−8 | 8.0 × 10−7 | 6.1 × 10−5 |
hsa-miR-30e-3p | 39.96 | −1.46 | −2.75 | 8.1 × 10−8 | 1.3 × 10−7 | 1.0 × 10−4 |
hsa-miR-28-3p | 140.84 | −0.86 | −1.81 | 8.6 × 10−8 | 1.3 × 10−7 | 1.1 × 10−4 |
hsa-miR-1468-5p | 2.40 | −2.33 | −5.02 | 1.7 × 10−7 | 2.6 × 10−7 | 2.2 × 10−4 |
hsa-miR-378i | 4.44 | −1.85 | −3.60 | 1.9 × 10−7 | 2.8 × 10−7 | 2.4 × 10−4 |
hsa-miR-625-3p | 86.60 | 1.37 | 2.58 | 3.7 × 10−7 | 5.3 × 10−7 | 4.7 × 10−4 |
hsa-miR-3065-5p | 4.52 | −1.96 | −3.90 | 3.8 × 10−7 | 5.4 × 10−7 | 4.8 × 10−4 |
hsa-miR-874-3p | 10.28 | −1.51 | −2.84 | 5.6 × 10−7 | 7.7 × 10−7 | 7.0 × 10−4 |
Assay | Max Groupmean | log2 Foldchange | Foldchange | p-Value | FDR p-Value | Bonferroni |
---|---|---|---|---|---|---|
hsa-miR-885-3p | 48.16 | −3.37 | −10.32 | 6.3 × 10−25 | 3.9 × 10−22 | 8.0 × 10−22 |
hsa-miR-885-5p | 70.76 | −2.71 | −6.53 | 2.2 × 10−19 | 6.5 × 10−17 | 2.8 × 10−16 |
hsa-miR-193b-5p | 46.92 | −2.74 | −6.68 | 3.2 × 10−19 | 6.5 × 10−17 | 4.0 × 10−16 |
hsa-miR-100-5p | 116.84 | −2.40 | −5.28 | 5.2 × 10−18 | 7.6 × 10−16 | 6.5 × 10−15 |
hsa-miR-34a-5p | 41.88 | −2.65 | −6.29 | 6.2 × 10−18 | 7.6 × 10−16 | 7.8 × 10−15 |
hsa-miR-192-5p | 1675.12 | −2.32 | −5.00 | 1.8 × 10−17 | 1.9 × 10−15 | 2.3 × 10−14 |
hsa-miR-148a-3p | 2186.08 | −1.60 | −3.02 | 2.3 × 10−17 | 2.0 × 10−15 | 2.8 × 10−14 |
hsa-miR-122-5p | 140,835.00 | −2.31 | −4.96 | 1.4 × 10−15 | 1.0 × 10−13 | 1.7 × 10−12 |
hsa-miR-194-5p | 600.92 | −1.97 | −3.93 | 1.6 × 10−15 | 1.1 × 10−13 | 2.0 × 10−12 |
hsa-miR-27b-3p | 295.20 | −1.47 | −2.77 | 1.1 × 10−14 | 6.6 × 10−13 | 1.4 × 10−11 |
hsa-miR-365a-3p | 21.28 | −2.51 | −5.70 | 1.7 × 10−14 | 9.4 × 10−13 | 2.1 × 10−11 |
hsa-miR-483-3p | 253.28 | −2.30 | −4.93 | 3.1 × 10−14 | 1.6 × 10−12 | 3.9 × 10−11 |
hsa-miR-23b-3p | 255.72 | −1.96 | −3.90 | 3.9 × 10−14 | 1.8 × 10−12 | 4.9 × 10−11 |
hsa-miR-125b-5p | 2728.28 | −1.84 | −3.57 | 6.0 × 10−14 | 2.6 × 10−12 | 7.5 × 10−11 |
hsa-miR-30a-3p | 45.40 | −2.18 | −4.54 | 6.3 × 10−14 | 2.6 × 10−12 | 8.0 × 10−11 |
hsa-miR-99a-5p | 179.40 | −1.93 | −3.80 | 1.7 × 10−13 | 6.6 × 10−12 | 2.1 × 10−10 |
hsa-miR-146b-5p | 175.20 | −1.91 | −3.75 | 4.3 × 10−13 | 1.6 × 10−11 | 5.5 × 10−10 |
hsa-miR-122-3p | 54.72 | −2.66 | −6.33 | 1.3 × 10−12 | 4.4 × 10−11 | 1.6 × 10−9 |
hsa-miR-146b-3p | 16.12 | −2.54 | −5.83 | 1.9 × 10−12 | 6.1 × 10−11 | 2.3 × 10−9 |
hsa-let-7c-5p | 1429.64 | −2.03 | −4.09 | 2.3 × 10−12 | 7.1 × 10−11 | 2.9 × 10−9 |
hsa-miR-194-3p | 8.08 | −3.78 | −13.76 | 4.8 × 10−12 | 1.4 × 10−10 | 6.1 × 10−9 |
hsa-miR-30c-5p | 122.72 | −1.24 | −2.37 | 5.4 × 10−12 | 1.5 × 10−10 | 6.8 × 10−9 |
hsa-miR-574-3p | 141.24 | −1.80 | −3.47 | 6.1 × 10−12 | 1.6 × 10−10 | 7.7 × 10−9 |
hsa-miR-125b-2-3p | 6.44 | −3.22 | −9.29 | 2.3 × 10−11 | 5.9 × 10−10 | 2.9 × 10−8 |
hsa-miR-378a-5p | 10.60 | −2.33 | −5.02 | 2.4 × 10−11 | 5.9 × 10−10 | 3.0 × 10−8 |
hsa-miR-30a-5p | 335.88 | −1.29 | −2.45 | 2.9 × 10−11 | 7.0 × 10−10 | 3.7 × 10−8 |
hsa-miR-455-5p | 10.16 | −2.66 | −6.31 | 1.4 × 10−9 | 3.2 × 10−8 | 1.8 × 10−6 |
hsa-miR-1468-5p | 4.40 | −2.44 | −5.44 | 8.6 × 10−9 | 1.9 × 10−7 | 1.1 × 10−5 |
hsa-miR-193a-5p | 133.12 | −1.04 | −2.06 | 1.3 × 10−8 | 2.7 × 10−7 | 1.6 × 10−5 |
hsa-miR-204-5p | 12.04 | −1.68 | −3.20 | 6.8 × 10−8 | 1.4 × 10−6 | 8.6 × 10−5 |
hsa-miR-345-5p | 25.48 | −1.24 | −2.36 | 8.5 × 10−8 | 1.7 × 10−6 | 1.1 × 10−4 |
hsa-miR-28-3p | 244.56 | −0.81 | −1.75 | 3.3 × 10−7 | 6.4 × 10−6 | 4.1 × 10−4 |
hsa-miR-99a-3p | 4.16 | −2.49 | −5.60 | 5.4 × 10−7 | 1.0 × 10−5 | 6.8 × 10−4 |
hsa-miR-455-3p | 4.08 | −2.40 | −5.28 | 6.3 × 10−7 | 1.2 × 10−5 | 8.0 × 10−4 |
ENI vs. CHD | ENI vs. CHB | |||
---|---|---|---|---|
Assay | Fold Change | Bonferroni | Fold Change | Bonferroni |
hsa-miR-204-5p | −3.20 | 8.60 × 10−05 | −2.89 | 3.16 × 10−03 |
hsa-miR-345-5p | −2.36 | 1.08 × 10−04 | −2.21 | 2.84 × 10−03 |
hsa-miR-99a-3p | −5.60 | 6.75 × 10−04 | −4.89 | 1.37 × 10−02 |
ENI vs. CHB | ENI vs. CHD | |||
---|---|---|---|---|
Assay | Fold Change | Bonferroni | Fold Change | Bonferroni |
hsa-miR-378a-3p | −2.78 | 1.32 × 10−10 | −1.90 | 3.18 × 10−03 |
hsa-miR-200a-3p | −7.05 | 1.56 × 10−09 | −2.04 | 1.00 |
hsa-miR-200b-3p | −7.37 | 1.64 × 10−08 | −2.90 | 4.34 × 10−01 |
hsa-miR-203a-3p | −3.59 | 4.31 × 10−05 | −3.02 | 1.44 × 10−03 |
hsa-miR-30e-3p | −2.75 | 1.03 × 10−04 | −2.46 | 1.67 × 10−03 |
hsa-miR-378i | −3.60 | 2.37 × 10−04 | −3.00 | 4.52 × 10−03 |
hsa-miR-3065-5p | −3.90 | 4.82 × 10−04 | −2.40 | 1.00 |
hsa-miR-874-3p | −2.84 | 7.03 × 10−04 | −2.19 | 1.39 × 10−01 |
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Cavallone, D.; Ornos, E.D.B.; Ricco, G.; Oliveri, F.; Coco, B.; Colombatto, P.; De Rosa, L.; Dalmacio, L.M.M.; Bonino, F.; Brunetto, M.R. The Circulating miRNA Profile of Chronic Hepatitis D and B Patients Is Comparable but Differs from That of Individuals with HBeAg-Negative HBV Infection. Viruses 2023, 15, 2257. https://doi.org/10.3390/v15112257
Cavallone D, Ornos EDB, Ricco G, Oliveri F, Coco B, Colombatto P, De Rosa L, Dalmacio LMM, Bonino F, Brunetto MR. The Circulating miRNA Profile of Chronic Hepatitis D and B Patients Is Comparable but Differs from That of Individuals with HBeAg-Negative HBV Infection. Viruses. 2023; 15(11):2257. https://doi.org/10.3390/v15112257
Chicago/Turabian StyleCavallone, Daniela, Eric David B. Ornos, Gabriele Ricco, Filippo Oliveri, Barbara Coco, Piero Colombatto, Laura De Rosa, Leslie Michelle M. Dalmacio, Ferruccio Bonino, and Maurizia Rossana Brunetto. 2023. "The Circulating miRNA Profile of Chronic Hepatitis D and B Patients Is Comparable but Differs from That of Individuals with HBeAg-Negative HBV Infection" Viruses 15, no. 11: 2257. https://doi.org/10.3390/v15112257
APA StyleCavallone, D., Ornos, E. D. B., Ricco, G., Oliveri, F., Coco, B., Colombatto, P., De Rosa, L., Dalmacio, L. M. M., Bonino, F., & Brunetto, M. R. (2023). The Circulating miRNA Profile of Chronic Hepatitis D and B Patients Is Comparable but Differs from That of Individuals with HBeAg-Negative HBV Infection. Viruses, 15(11), 2257. https://doi.org/10.3390/v15112257