{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:27:16Z","timestamp":1788535636491,"version":"build-2803163510"},"reference-count":58,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hepatitis C Virus (HCV), particularly genotype 3 (GT-3), is highly prevalent in India and is associated with faster progression to cirrhosis, hepatocellular carcinoma, and higher treatment failure rates. Although Direct-Acting Antivirals (DAAs) have revolutionized HCV therapy, 5\u201310% of patients fail to achieve sustained virological response (SVR). This proteomic study aimed to identify changes in the proteomic profile before and after treatment of both responders and non-responders to HCV treatment. Paired plasma samples from HCV GT-3 infected patients were collected before and 12 weeks after initiating DAAs treatment, along with healthy controls. Quantitative proteomic analysis was performed on the paired samples. Differentially expressed proteins (DEPs) were identified and subjected to functional analysis including gene set enrichment analysis (GSEA) and protein\u2013protein interaction (PPI) network analysis. GSEA revealed enrichment in extracellular matrix organization and innate immune pathways. Expression patterns of candidate proteins selected based on fold change and false discovery rate (FDR) criteria were further evaluated in an independent cohort. Western blot confirmed key expression trends of candidate proteins. Proteins linked to extracellular matrix remodeling and angiogenesis showed differential expression patterns. Successful validation of these candidate proteins in large independent cohorts holds potential to predict therapeutic outcomes.<\/jats:p>","DOI":"10.1021\/acs.jproteome.5c01003","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:02:32Z","timestamp":1786460552000},"page":"4448-4462","source":"Crossref","is-referenced-by-count":0,"title":["Differential\nProteomic Profiling of Responders and\nNon-responders to Direct-Acting Antivirals Treatment in Chronic Hepatitis\nC Virus Infection"],"prefix":"10.1021","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9537-2346","authenticated-orcid":true,"given":"Shreyasi","family":"Nath","sequence":"first","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwesha","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5588-5526","authenticated-orcid":true,"given":"Raina","family":"Das","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3332-2052","authenticated-orcid":true,"given":"Sagnik","family":"Bakshi","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2516-5146","authenticated-orcid":true,"given":"Supradip","family":"Dutta","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-6001","authenticated-orcid":true,"given":"Priya","family":"Verma","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uttaran","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6363-886X","authenticated-orcid":true,"given":"Upasana","family":"Baskey","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudipta","family":"Mondal","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik Kumar","family":"Dey","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7014-0530","authenticated-orcid":true,"given":"Provash Chandra","family":"Sadhukhan","sequence":"additional","affiliation":[{"name":"Indian Council of Medical Research-National Institute for Research in Bacterial Infections (formerly Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases) , P-33, Scheme XM, CIT Road, Beliaghata , , ,","place":["Kolkata, West Bengal, India, 700010"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"issue":"10","key":"2026090409132675900_cit1","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.4254\/wjh.v7.i10.1377","article-title":"Hepatitis C Virus: Virology, Diagnosis and Treatment","volume":"7","author":"Li","year":"2015","journal-title":"World J. Hepatol."},{"issue":"10207","key":"2026090409132675900_cit2","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1016\/S0140-6736(19)32320-7","article-title":"Hepatitis C","volume":"394","author":"Spearman","year":"2019","journal-title":"Lancet"},{"key":"2026090409132675900_cit3","unstructured":"Global Hepatitis Report 2024.\n          \n          Action for Access\nin Low- and Middle-Income\nCountries; World Health Organization, 2024."},{"issue":"3","key":"2026090409132675900_cit4","doi-asserted-by":"publisher","first-page":"ofz076","DOI":"10.1093\/ofid\/ofz076","article-title":"Identification\nof 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification","volume":"6","author":"Hedskog","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"2026090409132675900_cit5","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1002\/hep.27259\/suppinfo","article-title":"Global Distribution and Prevalence\nof Hepatitis C Virus Genotypes","volume":"61","author":"Messina","year":"2015","journal-title":"Hepatology"},{"issue":"5","key":"2026090409132675900_cit6","doi-asserted-by":"publisher","first-page":"445","DOI":"10.4103\/ijmr.IJMR_1850_16","article-title":"Genotyping & Diagnostic\nMethods for Hepatitis C Virus: A Need\nof Low-Resource Countries","volume":"147","author":"Kumar","year":"2018","journal-title":"Indian J. Med. Res."},{"key":"2026090409132675900_cit7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/liv.13673","article-title":"Treatment of Hepatitis C Virus Infection\nwith Direct-Acting Antiviral Agents: 100% Cure?","volume":"38","author":"Asselah","year":"2018","journal-title":"Liver Int."},{"key":"2026090409132675900_cit8","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1053\/j.gastro.2018.10.024","article-title":"Status of Direct-Acting\nAntiviral Therapy for HCV Infection and Remaining Challenges HHS Public\nAccess","volume":"156","author":"Baumert","year":"2019","journal-title":"Gastroenterology"},{"issue":"2","key":"2026090409132675900_cit9","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3390\/v17020269","article-title":"Efficacy\nof Different Combinations\nof Direct-Acting Antivirals Against Different Hepatitis C Virus-Infected\nPopulation Groups: An Experience in Tertiary Care Hospitals in West\nBengal, India","volume":"17","author":"Bakshi","year":"2025","journal-title":"Viruses"},{"issue":"1","key":"2026090409132675900_cit10","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1186\/s12879-025-11565-3","article-title":"Assessment of Direct-Acting Antiviral Treatment Outcomes\nin Patients with Chronic Hepatitis C Infected with Various HCV Genotypes:\nInsights from a Real-World Cohort in West Bengal, India","volume":"25","author":"Dutta","year":"2025","journal-title":"BMC Infect. Dis."},{"issue":"8","key":"2026090409132675900_cit11","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1016\/j.meegid.2012.07.010","article-title":"Hepatitis C Virus Entry:\nRole of Host and Viral Factors","volume":"12","author":"Samreen","year":"2012","journal-title":"Infect., Genet.\nEvol."},{"issue":"2","key":"2026090409132675900_cit12","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s40265-016-0685-x","article-title":"Genotype 3 Infection\u2013 The\nLast Stand of Hepatitis C Virus","volume":"77","author":"Chan","year":"2017","journal-title":"Drugs"},{"issue":"1","key":"2026090409132675900_cit13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.4103\/ijmr.IJMR_679_15","article-title":"Newer Direct-Acting\nAntivirals for Hepatitis C Virus Infection: Perspectives for India","volume":"146","author":"Gupta","year":"2017","journal-title":"Indian J. Med. Res."},{"key":"2026090409132675900_cit14","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s13337-020-00592-0","article-title":"HCV Genotypes\nand Their Determinative Role in Hepatitis C Treatment","volume":"31","author":"Keikha","year":"2020","journal-title":"VirusDisease"},{"issue":"22","key":"2026090409132675900_cit15","doi-asserted-by":"publisher","first-page":"8459","DOI":"10.26355\/EURREV_202211_30400","article-title":"Biochemical\nPredictors of Hepatocellular Cancer Development\nafter One Year in Patients Who Achieved HCV Clearance by Direct-Acting\nAntiviral Treatment","volume":"26","author":"Sargin","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol.\nSci."},{"issue":"2","key":"2026090409132675900_cit16","doi-asserted-by":"publisher","first-page":"463","DOI":"10.3390\/cancers15020463","article-title":"Thrombospondin-2\nas a Predictive Biomarker for Hepatocellular Carcinoma after Hepatitis\nC Virus Elimination by Direct-Acting Antiviral","volume":"15","author":"Matsumae","year":"2023","journal-title":"Cancers"},{"issue":"1","key":"2026090409132675900_cit17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12935-024-03600-1","article-title":"Novel Biomarkers\nfor Monitoring and Management of Hepatocellular\nCarcinoma","volume":"24","author":"Solhi","year":"2024","journal-title":"Cancer Cell Int."},{"issue":"2","key":"2026090409132675900_cit18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41419-021-03443-y","article-title":"Dynamically\nRemodeled Hepatic Extracellular Matrix Predicts Prognosis of Early-Stage\nCirrhosis","volume":"12","author":"Wu","year":"2021","journal-title":"Cell Death Dis."},{"issue":"1","key":"2026090409132675900_cit19","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1186\/s12885-022-10049-w","article-title":"Development and Validation\nof an\nECM-Related Prognostic Signature to Predict the Immune Landscape of\nHuman Hepatocellular Carcinoma","volume":"22","author":"Wu","year":"2022","journal-title":"BMC Cancer"},{"key":"2026090409132675900_cit20","doi-asserted-by":"publisher","first-page":"110861","DOI":"10.1016\/j.clinbiochem.2024.110861","article-title":"Exploratory Study of\nExtracellular Matrix Biomarkers for Non-Invasive Liver Fibrosis Staging:\nA Machine Learning Approach with XGBoost and Explainable AI","volume":"135","author":"Carnazzo","year":"2025","journal-title":"Clin. 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Oncol."},{"key":"2026090409132675900_cit23","unstructured":"Effect Size for before-after Study (Paired\nT-test) | Sample Size\nCalculators. https:\/\/sample-size.net\/effect-size-study-paired-t-test\/(accessed June, 06 2025)."},{"key":"2026090409132675900_cit24","unstructured":"Effect Size Calculator\n(Cohen\u2019s D) for T-Test. https:\/\/www.socscistatistics.com\/effectsize\/default3.aspx (accessed\nJune, 04 2025)."},{"key":"2026090409132675900_cit25","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.cyto.2017.10.026","article-title":"Association\nof TNF-Alpha (\u2212308 A\/G) and IFN-Gamma (+874 A\/T) Gene Polymorphisms\nin Response to Spontaneous and Treatment Induced Viral Clearance in\nHCV Infected Multitransfused Thalassemic Patients","volume":"106","author":"Biswas","year":"2018","journal-title":"Cytokine"},{"key":"2026090409132675900_cit26","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.meegid.2014.03.008","article-title":"Transmission\nDynamics of Hepatitis C Virus among Intra Venous Drug Users in the\nBorder State of Manipur, India","volume":"24","author":"Saha","year":"2014","journal-title":"Infect., Genet.\nEvol."},{"key":"2026090409132675900_cit27","unstructured":"Genotyping. https:\/\/www.ncbi.nlm.nih.gov\/projects\/genotyping\/formpage.cgi (accessed May, 02 2025)."},{"issue":"2","key":"2026090409132675900_cit28","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3390\/pathogens11020271","article-title":"Methods of\nInactivation of Highly\nPathogenic Viruses for Molecular, Serology or Vaccine Development\nPurposes","volume":"11","author":"Elveborg","year":"2022","journal-title":"Pathogens"},{"issue":"9","key":"2026090409132675900_cit29","doi-asserted-by":"publisher","first-page":"3731","DOI":"10.1021\/acs.jproteome.3c00751","article-title":"Differential\nProteomic Profiling at Different Phases of Dengue Infection: An Intricate\nInsight from Proteins to Pathogenesis","volume":"23","author":"Choudhury","year":"2024","journal-title":"J. Proteome\nRes."},{"issue":"1","key":"2026090409132675900_cit30","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s12967-019-1937-9","article-title":"Clinical Biomarker Discovery by SWATH-MS\nBased Label-Free\nQuantitative Proteomics: Impact of Criteria for Identification of\nDifferentiators and Data Normalization Method","volume":"17","author":"Narasimhan","year":"2019","journal-title":"J. Transl. Med."},{"issue":"6","key":"2026090409132675900_cit31","doi-asserted-by":"publisher","first-page":"3114","DOI":"10.1021\/pr401264n","article-title":"Normalyzer: A Tool for Rapid Evaluation\nof Normalization Methods for Omics Data Sets","volume":"13","author":"Chawade","year":"2014","journal-title":"J. Proteome Res."},{"issue":"3","key":"2026090409132675900_cit32","doi-asserted-by":"publisher","first-page":"279","DOI":"10.4300\/JGME-D-12-00156.1","article-title":"Using Effect Size\u2500or Why the P Value Is Not Enough","volume":"4","author":"Sullivan","year":"2012","journal-title":"J. Grad. Med. 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Commun."},{"issue":"8","key":"2026090409132675900_cit39","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1158\/2159-8290.CD-24-0002","article-title":"The Interplay between Extracellular Matrix Remodeling\nand Cancer Therapeutics","volume":"14","author":"Prakash","year":"2024","journal-title":"Cancer Discov."},{"issue":"6","key":"2026090409132675900_cit40","doi-asserted-by":"publisher","first-page":"665","DOI":"10.2174\/1389450054863662","article-title":"Decreasing the Metastatic\nPotential in Cancers - Targeting\nthe Heparan Sulfate Proteoglycans","volume":"6","author":"Fjeldstad","year":"2005","journal-title":"Curr. Drug\nTargets"},{"key":"2026090409132675900_cit41","doi-asserted-by":"publisher","first-page":"1432224","DOI":"10.3389\/fmed.2024.1432224","article-title":"The Function of\nthe Inter-Alpha-Trypsin Inhibitors\nin the Development of Disease","volume":"11","author":"Zhang","year":"2024","journal-title":"Front. Med."},{"issue":"8","key":"2026090409132675900_cit42","doi-asserted-by":"publisher","first-page":"11096","DOI":"10.18632\/aging.202765","article-title":"Pan-Cancer Analysis\nIdentifies ITIH1 as a Novel Prognostic Indicator\nfor Hepatocellular Carcinoma","volume":"13","author":"Chang","year":"2021","journal-title":"Aging"},{"key":"2026090409132675900_cit43","doi-asserted-by":"publisher","first-page":"100097","DOI":"10.1016\/j.bbiosy.2024.100097","article-title":"The Role of Extracellular\nMatrix in Angiogenesis: Beyond Adhesion and Structure","volume":"15","author":"Libby","year":"2024","journal-title":"Biomater. Biosyst."},{"issue":"7","key":"2026090409132675900_cit44","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1038\/s41390-020-01177-9","article-title":"The Role of\nIntegrins in Inflammation and Angiogenesis","volume":"89","author":"Mezu-Ndubuisi","year":"2021","journal-title":"Pediatr. Res."},{"issue":"1","key":"2026090409132675900_cit45","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0009-8981(96)06503-5","article-title":"Plasma Vitronectin\nConcentrations\nin Patients with Chronic Hepatitis C Treated with Interferon Alpha","volume":"261","author":"Yamada","year":"1997","journal-title":"Clin. Chim. Acta"},{"issue":"2","key":"2026090409132675900_cit46","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/iep.12306","article-title":"Vitronectin\nDeficiency\nAttenuates Hepatic Fibrosis in a Non-alcoholic Steatohepatitis-induced\nMouse Model","volume":"100","author":"Hayashida","year":"2019","journal-title":"Int. J. Exp. Pathol."},{"issue":"9","key":"2026090409132675900_cit47","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1002\/PMIC.201300422","article-title":"Spike-in SILAC\nProteomic Approach Reveals the Vitronectin as an Early Molecular Signature\nof Liver Fibrosis in Hepatitis C Infections with Hepatic Iron Overload","volume":"14","author":"Montaldo","year":"2014","journal-title":"Proteomics"},{"issue":"1","key":"2026090409132675900_cit48","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1186\/s12885-018-4532-1","article-title":"Dynamic Hyaluronan\nDrives Liver Endothelial Cells towards Angiogenesis","volume":"18","author":"Ghose","year":"2018","journal-title":"BMC Cancer"},{"issue":"2","key":"2026090409132675900_cit49","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s11010-024-05010-3","article-title":"Ang-1 and\nVEGF: Central Regulators of Angiogenesis","volume":"480","author":"Zhao","year":"2024","journal-title":"Mol.\nCell. 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