Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Bioinformatics Set Up
2.3. RNA Extraction
2.4. Reverse Transcription and Real-Time PCR (RT-qpcr)
2.5. Statistical Analysis
3. Results
3.1. NASH Association with Clinical and Biochemical Markers
3.2. Differential Expression of the NASH Predictors in the Study Groups
3.3. Correlation between NASH Predictors
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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Parameters | NAFLD without Steatosis n = 14 | NAFLD with Simple Steatosis n = 11 | NASH n = 55 | Healthy Control n = 80 | p Value |
---|---|---|---|---|---|
Sex | N/A | 0.785 | |||
male | 10 (71.4%) | 7 (63.6%) | 40 (72.7%) | 52 (65%) | |
female | 4 (28.6%) | 4 (36.4%) | 15 (27.3%) | 18 (35%) | |
History of diabetes mellitus | N/A | N/A | N/A | N/A | 0.00 ** |
positive | 13 (92.9%) | 9 (81.8%) | 46 (83.6%) | 27 (33.8%) | |
negative | 1 (7.1%) | 2 (18.2%) | 9 (16.4%) | 53 (66.3%) | |
Body mass index (kg/m2) BMI | 35.7 ± 4.2 | 35.4 ± 4.2 | 35.11 ± 6.1 | 25.99 ± 3.2 | a 0.00 b 0.00 c 0.677 |
Total cholesterol (mg/dL) | 285.14 ± 35.4 | 291.36 ± 43.2 | 300.91 ± 68.7 | 176.63 ± 84.9 | a 0.00 b 0.00 c 0.479 |
LDLc (mg/dL) | 200.14 ± 32.3 | 202.73 ± 35.2 | 212.31 ± 60.5 | 126.15 ± 64.5 | a 0.00 b 0.00 c 0.495 |
HDLc (mg/dL) | 34.64 ± 10 | 28.82 ± 7.3 | 28.80 ± 8.1 | 53.49 ± 20.9 | a 0.00 b 0.00 c 0.226 |
Total triglycerides (mg/dL) | 259.29 ± 76 | 268.18 ± 61.7 | 288.45 ± 74.8 | 163.91 ± 92.6 | a 0.00 ** b 0.00 ** c 0.247 |
albumin creatinie ratio | 23.43 ± 4.2 | 25.27 ± 4.38 | 24.22 ± 4.9 | 19.04 ± 6.8 | a 0.011 * b 0.00 ** c 0.655 |
AST (IU/L) | 58.85 ± 20.9 | 69.98 ± 39.3 | 74.43 ± 43.9 | 48.13 ± 18.9 | a 0.241 b 0.00 ** c 0.1 |
ALT (IU/L) | 37.21 ± 20 | 47.300 ± 24.28 | 57.78 ± 41.28 | 33.96 ± 16.4 | a 0.692 b 0.00 ** c 0.016 * |
Total bilirubin (mg/dL) | 2.01 ± 0.6 | 2.74 ± 0.4 | 2.9 ± 1 | 1.57 ± 1.3 | a 0.187 b 0.00 ** c 0.005 ** |
Direct bilirubin (mg/dL) | 1.21 ± 0.5 | 1.66 ± 0.2 | 1.7 ± 0.7 | 0.90 ± 0.4 | a 0.07 b 0.00 ** c 0.005 ** |
Albumin (g/dL) | 3.14 ± 0.2 | 2.48 ± 0.4 | 2.3 ± 0.4 | 3.23 ± 0.3 | a 0.443 b 0.00 ** c 0.00 ** |
Gamma glutammyl transferase (IU/L) | 38.73 ± 20.2 | 46 ± 26.4 | 73.9 ± 44.46 | 26.7 ± 20.76 | a 0.187 b 0.00 ** c 0.00 ** |
alpha fetoprotein | 81.17 ± 85.4 | 160.13 ± 124.67 | 341.85 ± 534 | 17.26 ± 30.8 | a 0.448 b 0.00 ** c 0.007 ** |
Fasting blood glucose (mg/dL) | 213.71 ± 87.5 | 183.18 ± 80.3 | 186.27 ± 83.7 | 143.02 ± 87 | a 0.005 ** b 0.004 ** c 0.286 |
Glycated hemoglobin HbA1c (%) | 6.32 ± 2.4 | 6.72 ± 1.7 | 7.7 ± 1.7 | 6.2 ± 2.7 | a 0.496 b 0.00 ** c 0.039 * |
HOMA IR | 6.5 ± 7.8 | 16.5 ± 8.1 | 18.15 ± 6.7 | 4.4 ± 6.1 | a 0.272 b 0.00 ** c 0.00 ** |
Scoring and Grading | |||||
NAFLD Score | N/A | N/A | N/A | --- | --- |
NAFLD Score < −1.455 = F0F2 | 13 (92.9%) | 7 (63.6%) | 1 (1.8%) | ||
NAFLD Score −1.455–0.675 | 1 (7.1%) | 3 (27.3%) | 6 (10.9%) | ||
NAFLD Score > 0.675 = F3F4 | 0 (0.0%) | 1 (2%) | 48 (98%) | ||
Fbrosis score | N/A | N/A | N/A | --- | --- |
F0 to F1 Mild liver scaring | 14 (100%) | 8 (72.7%) | 3 (5.5%) | ||
F2: Moderate liver scarring | 0 (0%) | 2 (18.2%) | 18 (32.7%) | ||
F3: Severe liver scarring | 0 (0%) | 0 (0%) | 24 (43.6%) | ||
F4: Advanced liver scarring (cirrhosis | 0 (0%) | 0 (0%) | 10 (18.2%) | ||
steatosis grading | N/A | N/A | N/A | --- | --- |
S1 mild steatosis | 0 (0.0%) | 10 (90.9%) | 1 (1.8%) | ||
S2 moderate stetosis | 0 (0.0%) | 1 (9.1%) | 19 (34.5%) | ||
S3 severe steatosis | 0 (0.0%) | 0 (0.0%) | 25 (63.6%) | ||
S4 non steatosis | 14 (100%) | 0 (0.0%) | 0 (0.0%) |
Test Result Variable(s) | Area under Curve | Std. Error | Asymptotic Sig | Asymptotic 95% Confidence Interval | ||||
---|---|---|---|---|---|---|---|---|
Lower Bound | Upper Bound | Cutoff | Sensitivity | Specificity | ||||
NAFLD versus healthy control | ||||||||
Relative quantity of lncRNA-SPARCL1-1:2 | 0.870 | 0.032 | 0.000 | 0.807 | 0.932 | 4.45 | 83.8% | 83.8 |
Relative quantity of miRNA-6881 | 0.891 | 0.025 | 0.000 | 0.842 | 0.940 | 1.65 | 90% | 72.5% |
Relative quantity of ITGB1 mRNA | 0.858 | 0.032 | 0.000 | 0.796 | 0.920 | 1.75 | 90% | 70% |
Relative quantity of MMP14 mRNA | 0.862 | 0.033 | 0.000 | 0.798 | 0.925 | 2.05 | 86.3 | 80 |
Relative quantity of HSPD1 mRNA | 0.897 | 0.025 | 0.000 | 0.847 | 0.947 | 2.65 | 88.8 | 76.2 |
ALT | 0.674 | 0.043 | 0.000 | 0.589 | 0.759 | 42 | 55% | 74% |
AST | 0.674 | 0.043 | 0.000 | 0.590 | 0.757 | 57 | 53.8% | 77.5% |
GGT | 0.790 | 0.035 | 0.000 | 0.722 | 0.858 | 42 | 61.3% | 82% |
NASH versus NAFLD | ||||||||
Relative quantity of lncRNA-SPARCL1-1:2 | 0.974 | 0.019 | 0.000 | 0.936 | 1.000 | 17.2 | 90% | 100 |
Relative quantity of miRNA-6881 | 0.916 | 0.040 | 0.000 | 0.838 | 0.994 | 24.8 | 70.9% | 93.2 |
Relative quantity of ITGB1 mRNA | 0.825 | 0.056 | 0.000 | 0.715 | 0.936 | 12.5 | 74% | 78% |
Relative quantity of MMP14 mRNA | 0.868 | 0.059 | 0.000 | 0.752 | 0.984 | 11.3 | 78.2% | 78% |
Relative quantity of HSPD1 mRNA | 0.939 | 0.029 | 0.000 | 0.883 | 0.995 | 5.3 | 89% | 93% |
NASH versus Simple steatosis | ||||||||
Relative quantity of lncRNA-SPARCL1-1:2 | 0.790 | 0.079 | 0.003 | 0.636 | 0.945 | 54.5 | 70% | 81% |
Relative quantity of miRNA-6881 | 0.823 | 0.077 | 0.001 | 0.672 | 0.974 | 24.6 | 72% | 83% |
Relative quantity of ITGB1 mRNA | 0.695 | 0.095 | 0.042 | 0.508 | 0.882 | 12.1 | 70% | 83% |
Relative quantity of MMP14 mRNA | 0.730 | 0.094 | 0.017 | 0.545 | 0.914 | 20.3 | 65% | 83% |
Relative quantity of HSPD1 mRNA | 0.712 | .096 | 0.027 | 0.525 | 0.900 | 9.4 | 85.5% | 63% |
Predictors | Sig. | Exp(B) | 95% C.I. for EXP(B) | |
---|---|---|---|---|
Lower | Upper | |||
sex | 0.683 | 1.254 | 0.423 | 3.713 |
NAFLD scoring | 0.000 | 54.828 | 9.483 | 317.015 |
grading of steatosis | 0.051 | 0.943 | 0.891 | 0.922 |
fibrosis scoring | 0.04 | 0.955 | 0.877 | 0.891 |
lncRNA-SPARCL1-1:2 | 0.006 | 0.958 | 0.929 | 0.988 |
miRNA-6881 | 0.046 | 0.964 | 0.930 | 0.999 |
ITGB1 mRNA | 0.087 | 1.014 | 0.998 | 1.029 |
MMP14 mRNA | 0.015 | 0.965 | 0.937 | 0.993 |
HSPD1 mRNA | 0.007 | 0.924 | 0.873 | 0.979 |
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Albadawy, R.; Agwa, S.H.A.; Khairy, E.; Saad, M.; El Touchy, N.; Othman, M.; Matboli, M. Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study. Biomedicines 2021, 9, 1248. https://doi.org/10.3390/biomedicines9091248
Albadawy R, Agwa SHA, Khairy E, Saad M, El Touchy N, Othman M, Matboli M. Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study. Biomedicines. 2021; 9(9):1248. https://doi.org/10.3390/biomedicines9091248
Chicago/Turabian StyleAlbadawy, Reda, Sara H. A. Agwa, Eman Khairy, Maha Saad, Naglaa El Touchy, Mohamed Othman, and Marwa Matboli. 2021. "Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study" Biomedicines 9, no. 9: 1248. https://doi.org/10.3390/biomedicines9091248