Cargando…

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

Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens—(hsa)-miR-21-5p, hsa-miR-155-5p...

Descripción completa

Detalles Bibliográficos
Autores principales: Eldosoky, Mona A., Hammad, Reham, Elmadbouly, Asmaa A., Aglan, Reda Badr, Abdel-Hamid, Sherihan G., Alboraie, Mohamed, Hassan, Donia Ahmed, Shaheen, Mohamed A., Rushdi, Areej, Ahmed, Reem M., Abdelbadea, Alzahra, Abdelmageed, Neamat A., Elshafei, Ahmed, Ali, Elham, Abo-Elkheir, Omaima I., Zaky, Samy, Hamdy, Nadia M., Lambert, Claude
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9962339/
https://www.ncbi.nlm.nih.gov/pubmed/36834570
http://dx.doi.org/10.3390/ijms24043157
_version_ 1784895980260294656
author Eldosoky, Mona A.
Hammad, Reham
Elmadbouly, Asmaa A.
Aglan, Reda Badr
Abdel-Hamid, Sherihan G.
Alboraie, Mohamed
Hassan, Donia Ahmed
Shaheen, Mohamed A.
Rushdi, Areej
Ahmed, Reem M.
Abdelbadea, Alzahra
Abdelmageed, Neamat A.
Elshafei, Ahmed
Ali, Elham
Abo-Elkheir, Omaima I.
Zaky, Samy
Hamdy, Nadia M.
Lambert, Claude
author_facet Eldosoky, Mona A.
Hammad, Reham
Elmadbouly, Asmaa A.
Aglan, Reda Badr
Abdel-Hamid, Sherihan G.
Alboraie, Mohamed
Hassan, Donia Ahmed
Shaheen, Mohamed A.
Rushdi, Areej
Ahmed, Reem M.
Abdelbadea, Alzahra
Abdelmageed, Neamat A.
Elshafei, Ahmed
Ali, Elham
Abo-Elkheir, Omaima I.
Zaky, Samy
Hamdy, Nadia M.
Lambert, Claude
author_sort Eldosoky, Mona A.
collection PubMed
description Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens—(hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p—expression levels as a panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), especially AFP-negative HCC cases, as a step toward non-protein coding (nc) RNA precision medicine. Subjects and methods: 79 patients enrolled with CHCV infection with LC, subclassified into an LC group without HCC (n = 40) and LC with HCC (n = 39). 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 the LC group (n = 40). hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin resistance (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%, respectively, vs. 69% for AFP alone, with acceptable specificities of 77.5%, 77.5%, and 80%, respectively, 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 specificities = 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]. Conclusions: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made it possible to identify HCC development in the 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 potential HCC molecular markers for AFP-negative HCC patients. hsa-miR-21-5p was linked, clinically and via in silico proof, to insulin metabolism, inflammation, dyslipidemia, and tumorigenesis in the HCC patients’ group as well as for an upregulated independent risk factor for the emergence of HCC from LC in the CHCV patients.
format Online
Article
Text
id pubmed-9962339
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-99623392023-02-26 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, Mona A. Hammad, Reham Elmadbouly, Asmaa A. Aglan, Reda Badr Abdel-Hamid, Sherihan G. Alboraie, Mohamed Hassan, Donia Ahmed Shaheen, Mohamed A. Rushdi, Areej Ahmed, Reem M. Abdelbadea, Alzahra Abdelmageed, Neamat A. Elshafei, Ahmed Ali, Elham Abo-Elkheir, Omaima I. Zaky, Samy Hamdy, Nadia M. Lambert, Claude Int J Mol Sci Article Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens—(hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p—expression levels as a panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), especially AFP-negative HCC cases, as a step toward non-protein coding (nc) RNA precision medicine. Subjects and methods: 79 patients enrolled with CHCV infection with LC, subclassified into an LC group without HCC (n = 40) and LC with HCC (n = 39). 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 the LC group (n = 40). hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin resistance (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%, respectively, vs. 69% for AFP alone, with acceptable specificities of 77.5%, 77.5%, and 80%, respectively, 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 specificities = 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]. Conclusions: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made it possible to identify HCC development in the 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 potential HCC molecular markers for AFP-negative HCC patients. hsa-miR-21-5p was linked, clinically and via in silico proof, to insulin metabolism, inflammation, dyslipidemia, and tumorigenesis in the HCC patients’ group as well as for an upregulated independent risk factor for the emergence of HCC from LC in the CHCV patients. MDPI 2023-02-05 /pmc/articles/PMC9962339/ /pubmed/36834570 http://dx.doi.org/10.3390/ijms24043157 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Eldosoky, Mona A.
Hammad, Reham
Elmadbouly, Asmaa A.
Aglan, Reda Badr
Abdel-Hamid, Sherihan G.
Alboraie, Mohamed
Hassan, Donia Ahmed
Shaheen, Mohamed A.
Rushdi, Areej
Ahmed, Reem M.
Abdelbadea, Alzahra
Abdelmageed, Neamat A.
Elshafei, Ahmed
Ali, Elham
Abo-Elkheir, Omaima I.
Zaky, Samy
Hamdy, Nadia M.
Lambert, Claude
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9962339/
https://www.ncbi.nlm.nih.gov/pubmed/36834570
http://dx.doi.org/10.3390/ijms24043157
work_keys_str_mv AT eldosokymonaa diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT hammadreham diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT elmadboulyasmaaa diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT aglanredabadr diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT abdelhamidsherihang diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT alboraiemohamed diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT hassandoniaahmed diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT shaheenmohameda diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT rushdiareej diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT ahmedreemm diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT abdelbadeaalzahra diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT abdelmageedneamata diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT elshafeiahmed diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT alielham diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT aboelkheiromaimai diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT zakysamy diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT hamdynadiam diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients
AT lambertclaude diagnosticsignificanceofhsamir215phsamir1925phsamir1555phsamir199a5ppanelandratiosinhepatocellularcarcinomaontopoflivercirrhosisinhcvinfectedpatients