{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:04:09Z","timestamp":1760148249170,"version":"build-2065373602"},"reference-count":17,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Minister of Science and Higher Education","award":["002\/RID\/2018\/19","UMO-2020\/37\/B\/NZ7\/01466"],"award-info":[{"award-number":["002\/RID\/2018\/19","UMO-2020\/37\/B\/NZ7\/01466"]}]},{"name":"the National Science Centre, Cracow, Poland","award":["002\/RID\/2018\/19","UMO-2020\/37\/B\/NZ7\/01466"],"award-info":[{"award-number":["002\/RID\/2018\/19","UMO-2020\/37\/B\/NZ7\/01466"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Given the substantial correlation between early diagnosis and prolonged patient survival in HCV patients, it is vital to identify a reliable and accessible biomarker. The purpose of this research was to identify accurate miRNA biomarkers to aid in the early diagnosis of HCV and to identify key target genes for anti-hepatic fibrosis therapeutics. The expression of 188 miRNAs in 42 HCV liver patients with different functional states and 23 normal livers were determined using RT-qPCR. After screening out differentially expressed miRNA (DEmiRNAs), the target genes were predicted. To validate target genes, an HCV microarray dataset was subjected to five machine learning algorithms (Random Forest, Adaboost, Bagging, Boosting, XGBoost) and then, based on the best model, importance features were selected. After identification of hub target genes, to evaluate the potency of compounds that might hit key hub target genes, molecular docking was performed. According to our data, eight DEmiRNAs are associated with early stage and eight DEmiRNAs are linked to a deterioration in liver function and an increase in HCV severity. In the validation phase of target genes, model evaluation revealed that XGBoost (AUC = 0.978) outperformed the other machine learning algorithms. The results of the maximal clique centrality algorithm determined that CDK1 is a hub target gene, which can be hinted at by hsa-miR-335, hsa-miR-140, hsa-miR-152, and hsa-miR-195. Because viral proteins boost CDK1 activation for cell mitosis, pharmacological inhibition may have anti-HCV therapeutic promise. The strong affinity binding of paeoniflorin (\u22126.32 kcal\/mol) and diosmin (\u22126.01 kcal\/mol) with CDK1 was demonstrated by molecular docking, which may result in attractive anti-HCV compounds. The findings of this study may provide significant evidence, in the context of the miRNA biomarkers, for early-stage HCV diagnosis. In addition, recognized hub target genes and small molecules with high binding affinity may constitute a novel set of therapeutic targets for HCV.<\/jats:p>","DOI":"10.3390\/ijms24087207","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T02:28:12Z","timestamp":1681439292000},"page":"7207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Mixture Method for Robust Detection HCV Early Diagnosis Biomarker with ML Approach and Molecular Docking"],"prefix":"10.3390","volume":"24","author":[{"given":"Maryam","family":"Gholizadeh","sequence":"first","affiliation":[{"name":"Institute for Bioinformatics, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-0687","authenticated-orcid":false,"given":"Joanna","family":"\u0141apczuk-Roma\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariola","family":"Post","sequence":"additional","affiliation":[{"name":"Department of General and Transplantation Surgery, County Hospital, 71-455 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Komaniecka","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed Reza","family":"Mazlooman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2359-2294","authenticated-orcid":false,"given":"Lars","family":"Kaderali","sequence":"additional","affiliation":[{"name":"Institute for Bioinformatics, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-7168","authenticated-orcid":false,"given":"Marek","family":"Dro\u017adzik","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13596535221083179","DOI":"10.1177\/13596535221083179","article-title":"Polaris Observatory\u2014Supporting informed decision-making at the national, regional, and global levels to eliminate viral hepatitis","volume":"27","author":"Razavi","year":"2022","journal-title":"Antivir. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13596535221083179","DOI":"10.1001\/jamanetworkopen.2022.45424","article-title":"Characteristics and Treatment Rate of Patients with Hepatitis C Virus Infection in the Direct-Acting Antiviral Era and During the COVID-19 Pandemic in the United States","volume":"5","author":"Nguyen","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100233","DOI":"10.1016\/j.jhepr.2021.100233","article-title":"Profiling circulating microRNAs in patients with cirrhosis and acute-on-chronic liver failure","volume":"3","author":"Blaya","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.5114\/aoms.2019.86621","article-title":"MicroRNA-122a as a non-invasive biomarker for HCV genotype 4-related hepatocellular carcinoma in Egyptian patients","volume":"15","author":"Mourad","year":"2019","journal-title":"Arch. Med. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.1002\/jmv.26999","article-title":"miRNA expression profiles in liver grafts of HCV and HIV\/HCV-infected recipients, 6 months after liver transplantation","volume":"93","author":"Bulfoni","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25151355221106104","DOI":"10.1177\/25151355221106104","article-title":"The involvement of microRNAs in HCV and HIV infection","volume":"10","author":"Joshi","year":"2022","journal-title":"Ther. Adv. Vaccines Immunother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41598-019-56630-5","article-title":"MicroRNA profiles in serum samples from Acute-On-Chronic Liver Failure patients and miR-25-3p as a potential biomarker for survival prediction","volume":"10","author":"Cisilotto","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101983","DOI":"10.1016\/j.jbc.2022.101983","article-title":"microRNA-27b regulates hepatic lipase enzyme LIPC and reduces triglyceride degradation during hepatitis C virus infection","volume":"298","author":"Desrochers","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"864839","DOI":"10.3389\/fmolb.2022.864839","article-title":"Implication of miR-122, miR-483, and miR-335 Expression Levels as Potential Signatures in HCV-Related Hepatocellular Carcinoma (HCC) in Egyptian Patients","volume":"9","author":"Elfert","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pascut, D., Hoang, M., Nguyen, N.N.Q., Pratama, M.Y., and Tiribelli, C. (2021). HCV Proteins Modulate the Host Cell miRNA Expression Contributing to Hepatitis C Pathogenesis and Hepatocellular Carcinoma Development. Cancers, 13.","DOI":"10.3390\/cancers13102485"},{"key":"ref_11","first-page":"486","article-title":"The interaction between microRNA-152 and DNA methyltransferase-1 as an epigenetic prognostic biomarker in HCV-induced liver cirrhosis and HCC patients","volume":"27","author":"Khalifa","year":"2022","journal-title":"Cancer Gene Ther."},{"key":"ref_12","first-page":"213","article-title":"Serum MiRNA-122 as a Diagnostic Marker in HCV Related Liver Cirrhosis","volume":"19","author":"Ahmed","year":"2020","journal-title":"Afro Egypt J. Infect. Endem. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.gendis.2019.04.007","article-title":"HCV infection causes cirrhosis in human by step-wise regulation of host genes involved in cellular functioning and defense during fibrosis: Identification of bio-markers","volume":"6","author":"Ijaz","year":"2019","journal-title":"Genes Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/hep.21608","article-title":"Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology","volume":"45","author":"Ng","year":"2007","journal-title":"Hepatology"},{"key":"ref_15","first-page":"6815","article-title":"Identification and functional analysis of a core gene module associated with hepatitis C virus-induced human hepatocellular carcinoma progression","volume":"15","author":"Bai","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10983","DOI":"10.1074\/jbc.M512536200","article-title":"Role of p38 MAPK and RNA-dependent protein kinase (PKR) in hepatitis C virus core-dependent nuclear delocalization of cyclin B1","volume":"281","author":"Spaziani","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_17","first-page":"281","article-title":"Random Search for Hyper-Parameter Optimization","volume":"13","author":"Bergstra","year":"2012","journal-title":"J. Mach. Learn. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7207\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:15:31Z","timestamp":1760123731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,13]]},"references-count":17,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24087207"],"URL":"https:\/\/doi.org\/10.3390\/ijms24087207","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,4,13]]}}}