Diagnostic accuracy of serum derived exosomes for hepatocellular carcinoma: a systematic review and meta-analysis

ABSTRACTIntroduction Early and non-invasive detection of hepatocellular carcinoma (HCC), which is usually asymptomatic, can improve overall survival outcomes. The objective of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of serum-derived exosomes for diagnosing HCC.Methods PubMed, Web of Science, and Scopus databases were searched for relevant studies up to April 2023. The quality of included studies was assessed using the QUADAS-2 checklist, and data were extracted. Statistical analysis was performed on 18 studies from 3,993 records, and a diagnostic meta-analysis was conducted. Biomarkers were categorized into four groups based on their type (exosomal miRNAs, exosomal RNAs, alpha-fetoprotein (AFP), and exosomal RNAs+AFP panel), and a meta-analysis was conducted for each category separately.Results The highest pooled sensitivity was 0.86 for exosomal miRNAs, and exosomal RNAs+AFP had the highest pooled specificity; (0.89). Furthermore, exosomal RNAs+AFP had the highest pooled positive likelihood ratio; (7.55), the highest pooled diagnostic odds ratio (35.96) and the highest pooled area under the curve (0.93). Exosomal miRNAs had the lowest pooled negative likelihood ratio; (0.17).Conclusions The diagnostic accuracy of exosomal biomarkers is superior to that of AFP, and combining the two in a panel yields the better results.KEYWORDS: Hepatocellular carcinomaexosomesdiagnosisextracellular vesiclesmeta-analysisbiomarkers Article highlights Our findings suggest that exosomal RNA biomarkers demonstrate superior diagnostic accuracy compared to AFP, and combining these two biomarkers yields the better results.The use of a panel consisting of exosomal RNAs and AFP results in a high level of diagnostic accuracy for HCC, with 82% sensitivity and 89% specificity.Among the different types of biomarkers, the combination of exosomal RNAs with AFP yielded the highest pooled diagnostic odds ratio (DOR) of 35.96.Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Author contributionsConception and design of the study: D Jafari. Acquisition of data: D Jafari, A Tiyuri, SS Baghermanesh. Analysis and/or interpretation: A Tiyuri, D Jafari. Drafting the manuscript: Davod Jafari, A Tiyuri, SS Baghermanesh, S Sadegh Eslami. Revising the manuscript critically for important intellectual content: All authors critically reviewed the manuscript for important intellectual content and provided their consent for publication.Data availability statementInput data for the analyses are available from the corresponding author on request.Ethics approval and consent to participateThis study has been approved by Research ethics committee of Iran university of Medical Sciences (#IR.IUMS.REC.1397.1141).AcknowledgmentsThe authors acknowledge Systematic Review Network of Vice-Chancellor for Research and Technology support at Iran University of Medical Sciences.Supplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2023.2260306.Additional informationFundingThis study was funded by Student Research Committee, Iran University of Medical Sciences [Grant Number: 13238].