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Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on top of Liver Cirrhosis in HCV Infected Patients
Eldosoky, M.A.; Hammad, R.; Elmadbouly, A.A.; Aglan, R.B.; Abdel-Hamid, S.G.; Alboraie, M.; Hassan, D.A.; Shaheen, M.A.; Rushdi, A.; Ahmed, R.M.; Abdelbadea, A.; Abdelmageed, N.A.; Elshafei, A.; Ali, E.; Abo-Elkheir, O.I.; Zaky, S.; Hamdy, N.M.; Lambert, C. Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients. Int. J. Mol. Sci.2023, 24, 3157.
Eldosoky, M.A.; Hammad, R.; Elmadbouly, A.A.; Aglan, R.B.; Abdel-Hamid, S.G.; Alboraie, M.; Hassan, D.A.; Shaheen, M.A.; Rushdi, A.; Ahmed, R.M.; Abdelbadea, A.; Abdelmageed, N.A.; Elshafei, A.; Ali, E.; Abo-Elkheir, O.I.; Zaky, S.; Hamdy, N.M.; Lambert, C. Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients. Int. J. Mol. Sci. 2023, 24, 3157.
Eldosoky, M.A.; Hammad, R.; Elmadbouly, A.A.; Aglan, R.B.; Abdel-Hamid, S.G.; Alboraie, M.; Hassan, D.A.; Shaheen, M.A.; Rushdi, A.; Ahmed, R.M.; Abdelbadea, A.; Abdelmageed, N.A.; Elshafei, A.; Ali, E.; Abo-Elkheir, O.I.; Zaky, S.; Hamdy, N.M.; Lambert, C. Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients. Int. J. Mol. Sci.2023, 24, 3157.
Eldosoky, M.A.; Hammad, R.; Elmadbouly, A.A.; Aglan, R.B.; Abdel-Hamid, S.G.; Alboraie, M.; Hassan, D.A.; Shaheen, M.A.; Rushdi, A.; Ahmed, R.M.; Abdelbadea, A.; Abdelmageed, N.A.; Elshafei, A.; Ali, E.; Abo-Elkheir, O.I.; Zaky, S.; Hamdy, N.M.; Lambert, C. Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients. Int. J. Mol. Sci. 2023, 24, 3157.
Abstract
Hepatocellular carcinoma (HCC) early diagnosis is challenging. Moreover, for patients with al-pha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profile may serve as potential HCC molecular markers. We aimed to assess plasma homo sabines (hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, hsa-miR-199a-5p expression levels, as panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), es-pecially AFP-negative HCC cases, a step toward non-protein coding (nc) RNA precision medicine. Subjects and Methods: 79 patients enrolled with CHCV infection with LC, subclassified into LC group without HCC (n=40) and LC with HCC (n=39) in comparison with 15 apparently healthy control subjects. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. Results: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n=39) when compared to LC group (n=40). Hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin re-sistance (r=0.5, p<0.001, r=0.334, p=0.01, and r=0.303, p=0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, re-spectively, vs 69% for AFP alone, with an acceptable specificity of 77.5%, 77.5%, and 80%, respec-tively, and AUC= 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC=0.76 and 0.71, respectively, with sensitivities=94% and 92%, and specifici-ties=48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR=1.198(1.063–1.329), p=0.002]. Conclusion: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made possi-ble to identify HCC development in LC patients’ cohort with higher sensitivity than using AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are poten-tial HCC molecular markers for AFP-negative HCC patients. Hsa-miR-21-5p was linked to insu-lin metabolism in HCC patients’ group as well as being an upregulated independent risk factor for the emergence of HCC from LC in CHCV patients.
Medicine and Pharmacology, Oncology and Oncogenics
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