Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals
Abstract
:1. Introduction
2. Results
2.1. Characteristics of the Study Population
2.2. Changes in Circulating miRNA after DAA Therapy
2.3. MicroRNA Screening in the Discovery Cohort, Identification of Predictive miRNA
2.4. Differential miRNA Expression Profiles and Identification of miRNA Biomarker Candidates
2.5. MiR-3197 as Diagnostic Biomarker
3. Discussion
4. Materials and Methods
4.1. Patient Characteristics
4.2. Study Design
4.3. Serum Collection and RNA Extraction
4.4. Microarray Profiling
4.5. Quantitative Real Time PCR (RT-qPCR)
4.6. Microarray Data Analysis
4.7. Statistical Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics | Study Group | § p-Level | ||
---|---|---|---|---|
Overall 40 Patients | Discovery 10 Patients | Validation 30 Patients | ||
Age, (years ± SD) | 56.3 ± 10.3 | 59.4 ± 6.3 | 55.0 ± 11.1 | 0.07 |
Gender male/female, (% males) | 26/14 (67.5) | 6/4 (70) | 20/10 (66.6) | 0.84 |
BMI, (kg/m2 ± SD) | 25.8 ± 3.1 | 27.3 ± 2.8 | 25.3 ± 3.1 | 0.08 |
Genotype HCV-1/non-1, (% HCV-1) | 27/13 (67.5) | 6/4 (60) | 21/9 (70) | 0.84 |
Child-Pugh score A5/A6-B7, (% A5) | 30/10 (75) | 8/2 (80) | 22/8 (73.3) | 1.0 |
Naive/Experienced, (% naive) | 13/27 (32.5) | 1/9 (10) | 12/18 (40) | 0.17 |
Sofosbuvir-based schedule, (%) | 35/5 (87.5) | 8/2 (80) | 27/3 (90) | 0.91 |
Ribavirin combination use, (%) | 38/2 (95) | 10/0 (100) | 28/2 (93.3) | 1.0 |
Treatment duration, (weeks ± SD) | 18.3 ± 5.6 | 20.4 ± 5.1 | 18.6 ± 5.6 | 0.16 |
SVR/Relapse, (% SVR) | 32/8 (80) | 7/3 (70) | 25/5 (83.3) | 0.64 |
ALT (U/L ± SD) | 114.9 ± 79.1 | 103.7 ± 87.6 | 110.2 ± 76.5 | 0.56 |
Albumin (mg/dL ± SD) | 40.9 ± 3.4 | 41.1 ± 3.5 | 39.2 ±3.4 | 0.15 |
Bilirubin (μmol/L ± SD) | 15.7 ± 7.1 | 14.5 ± 6.2 | 16.2 ± 8.3 | 0.36 |
PT (INR ± SD) | 1.1 ± 0.08 | 1.0 ± 0.05 | 1.1 ± 0.09 | 0.76 |
PLTS (×109/L ± SD) | 164 ± 110 | 120 ± 70 | 179 ± 120 | 0.61 |
Alfa-fetoprotein (μg/L ± SD) | 19 ± 32 | 17 ± 11 | 21 ± 36 | 0.14 |
HCC development, (%) | 20 (50) | 5 (50) | 15 (50) | 0.71 |
Time to HCC diagnosis from begin of DAAs (months ± SD) | 8.9 ± 5.6 | 9.2 ± 5.1 | 8.8 ± 5.6 | 0.8 |
miRNA | With HCC Mean Cq (95% CI) | With HCC Mean ΔΔCq (95% CI) | Without HCC Mean Cq (95% CI) | Without HCC Mean ΔΔCq (95% CI) |
---|---|---|---|---|
miR-483-5p | 35.83 (35.19–36.47) | 1.04 (0.62–1.47) | 36.22 (35.60–36.83) | 0.80 (0.51–1.10) |
miR-1246 | 31.56 (31.06–32.06) | 0.48 (0.34–0.63) | 31.94 (31.50–32.38) | 0.42 (0.24–0.61) |
miR-1180-3p | 33.41 (29.39–37.42) | 0.37 (0.13–0.62) | 32.77 (28.18–37.35) | 0.18 (0.12–0.24) |
miR-3197 | 36.00 (35.38–36.63) | 0.33 (0.14–0.52) | 34.46 (33.89–35.01) | 0.80 (0.48–1.12) |
miR-4443 | 27.75 (22.35–33.15) | 0.14 (0.04–0.24) | 26.71 (20.24–33.18) | 0.10 (0.07–0.14) |
miR-3178 | 33.70 (33.20–34.21) | 2.61 (2.12–3.12 | 34.34 (33.82–34.85) | 2.01 (1.48–2.53) |
miR-1207-5p | 31.07 (28.91–33.23) | 0.62 (0.46–0.79) | 32.02 (31.48–32.57) | 0.81 (0.51–1.12) |
miR-1228-3p | 26.83 (26.59–27.07) | 0.71 (0.42–0.99) | 26.42 (26.14–26.71) | 0.97 (0.71–1.2) |
miR-4484 | 32.5 (31.58–33.43) | 0.66 (0.43–0.88) | 32.97 (32.56–33.38) | 0.42 (0.33–0.51) |
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Share and Cite
Pascut, D.; Cavalletto, L.; Pratama, M.Y.; Bresolin, S.; Trentin, L.; Basso, G.; Bedogni, G.; Tiribelli, C.; Chemello, L. Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals. Cancers 2019, 11, 1773. https://doi.org/10.3390/cancers11111773
Pascut D, Cavalletto L, Pratama MY, Bresolin S, Trentin L, Basso G, Bedogni G, Tiribelli C, Chemello L. Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals. Cancers. 2019; 11(11):1773. https://doi.org/10.3390/cancers11111773
Chicago/Turabian StylePascut, Devis, Luisa Cavalletto, Muhammad Yogi Pratama, Silvia Bresolin, Luca Trentin, Giuseppe Basso, Giorgio Bedogni, Claudio Tiribelli, and Liliana Chemello. 2019. "Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals" Cancers 11, no. 11: 1773. https://doi.org/10.3390/cancers11111773