{"title":"Development of a Recombinant Outer Membrane Vesicles (OMVs)-Based Vaccine Against Helicobacter pylori Infection in Mice","authors":"Qiong Liu, Biaoxian Li, Jinrong Ma, Xiao Lei, Junpeng Ma, Yanyan Da, Zhiyong Zhou, Jiaqi Tao, Xinyi Ren, Ting Zeng, Zhiting Xie, Haiyan Lin, Zihui Jin, Yi Wan, Liang Zhang, Donglin Lai, Yaping Guo, Jing Li, Yinpan Shang, Lu Shen, Ziwei Tao, Tian Gong, Chengsheng Zhang","doi":"10.1002/jev2.70085","DOIUrl":"https://doi.org/10.1002/jev2.70085","url":null,"abstract":"<p>The current vaccine development for <i>Helicobacter pylori</i> (<i>H. pylori</i>) still faces challenges of weak immune responses stimulated by existing antigens and a lack of safe adjuvants. The modification of the lipopolysaccharide (LPS) structure by <i>H. pylori</i> is an important mechanism involved in its immune escape. In this study, we developed a novel recombinant vaccine candidate against <i>H. pylori</i> infection by knocking down the key genes (lpxE, lpxF and futB) of LPS modification and employing the bacterial outer membrane vesicles (OMVs) as a vector for delivering UreB, VacA and CagA antigens, and then evaluated its safety and immune protective efficacy in vitro and in vivo mouse model. We measured the antibody and cytokine productions, detected the subtypes of immune cells, and examined the histopathological changes in mice from the control and various experimental groups. We revealed that this OMV-based recombinant vaccine candidate could induce specific humoral immune responses and a Th1/Th2/Th17 mixed immune response, with Th17 being predominant, and markedly protect the mice from <i>H. pylori</i> infection. Our findings suggest that the OMVs with the genetically engineered LPS may function as a vector for delivering recombinant antigens and safe adjuvants for the development of novel vaccine candidates against <i>H. pylori</i> infection.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Palwasha Baryalai, David Irenaeus, Eric Toh, Madeleine Ramstedt, Bernt Eric Uhlin, Aftab Nadeem, Sun Nyunt Wai
{"title":"Hemagglutinin Protease HapA Associated With Vibrio cholerae Outer Membrane Vesicles (OMVs) Disrupts Tight and Adherens Junctions","authors":"Palwasha Baryalai, David Irenaeus, Eric Toh, Madeleine Ramstedt, Bernt Eric Uhlin, Aftab Nadeem, Sun Nyunt Wai","doi":"10.1002/jev2.70092","DOIUrl":"https://doi.org/10.1002/jev2.70092","url":null,"abstract":"<p>This study explores the virulence mechanisms of <i>Vibrio cholerae</i>, with a particular emphasis on HapA, a zinc metalloprotease delivered via outer membrane vesicles (OMVs). The findings reveal that OMV-associated HapA disrupts the integrity of tight and adherens junctions in intestinal epithelial cell models more effectively than its purified counterpart, suggesting that association with OMVs substantially potentiates the pathogenic effects of HapA. The study further details the uptake of <i>V. cholerae</i> OMVs by epithelial cells, as well as their targeted degradation of key junctional proteins, including claudin, ZO-1, and β-catenin. These results highlight the critical role of OMV-associated HapA in compromising epithelial barrier function. Additionally, the use of spheroids and intestinal organoids in our experiments provides deeper insight into bacterial pathogenesis, offering valuable information for the development of targeted therapeutic strategies.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hong-Dien Phan, Kaitlyn E. Mayne, Willow R. B. Squires, Grant R. Kelly, Reilly H. Smith, Rashid Jafardoust, Sherri L. Christian
{"title":"CD24 Regulates the Formation of Ectosomes in B Lymphocytes","authors":"Hong-Dien Phan, Kaitlyn E. Mayne, Willow R. B. Squires, Grant R. Kelly, Reilly H. Smith, Rashid Jafardoust, Sherri L. Christian","doi":"10.1002/jev2.70093","DOIUrl":"https://doi.org/10.1002/jev2.70093","url":null,"abstract":"<p>CD24 is a glycophosphatidylinositol-linked protein that regulates B cell development. We previously reported that stimulation of CD24 on donor B cells promotes the transfer of functional receptors to recipient B cells via extracellular vesicles (EVs). However, the mechanisms regulating CD24-mediated formation of bioactive EVs are unknown. Using bioinformatics, we found a connection between CD24, and PI3K/AKT, tran and mTOR. To determine if these pathways regulate EV release, we used flow cytometry to follow the transfer of EVs carrying lipid-associated GFP and surface IgM from donor to recipient B cells. Using chemical and genetic inhibition, we found that a PI3K/mTORC2/ROCK/actin pathway regulates bioactive EV formation via activation of acid sphingomyelinase (aSMase) upstream of PI3K. Using single EV analysis, we found that CD24 regulates the formation of the subset of bioactive EVs that are taken up by recipient cells and not total EVs. Interestingly, we also found that ROCK and aSMase modulate ectosome but not exosome formation, when CD24 is stimulated. Lastly, through live cell imaging, we found that PI3K and ROCK are required for inducing membrane dynamics associated with EV formation. These data suggest that this pathway regulates bioactive EV release that, in turn, could regulate B cell development.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Extracellular Vesicle (EV) Targeted Cells Release Secondary Effector EVs: Indication of How To Account for Histocompatibility and Disease Specificity of EV Treatments","authors":"Philip W. Askenase","doi":"10.1002/jev2.70076","DOIUrl":"https://doi.org/10.1002/jev2.70076","url":null,"abstract":"<p>The central hypothesis presented here is that released extracellular vesicles (EVs) can act primarily on targeted cells to induce the production of secondary EVs to mediate the final biological events. Compared here are different instances. In one, EVs, primarily produced by CD8<sup>+</sup> suppressor T cells, are activated in immune tolerance. These EVs transfer to companion recipient macrophages (Macs) the ability to generate production of secondary inhibitory EVs that affect the final-acting effector T cells. In a second instance of treating spinal cord injury (SCI), primary-acting mesenchymal stromal cell (MSC)-derived EVs target local tissue M2-type Macs to release secondary EVs that subsequently affect the local neuro microvasculature to mediate healing. Thus, these are very different systems acting similarly in this way. Per treatments with Mesenchymal Stromal Cells (MSCs), our proposal explains how their released EVs can act across tissue histocompatibility barriers and exhibit a seeming “disease specificity,” resulting in the healing of many diverse injuries and a wide variety of pathologic conditions. It is postulated that the recipients of the primary EVs, the secondarily acting cells, are often but not exclusively Macs. These are among the local responding secondary-acting cells that produce transplantation-matched EVs. Further, the secondary-acting MSC-derived primary EVs that are clinically active in many diverse instances led to the additional hypothesis that secondary EVs produced by targeted local cells may be appropriate to each specific instance to explain such disease specificity. We propose that there may be many other examples to be uncovered in which primary EVs similarly induce secondary EV healing effects.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benjamin L. Koch, Brian D. Rutter, M. Lucía Borniego, Meenu Singla-Rastogi, Dillon M. Gardner, Roger W. Innes
{"title":"Arabidopsis Produces Distinct Subpopulations of Extracellular Vesicles That Respond Differentially to Biotic Stress, Altering Growth and Infectivity of a Fungal Pathogen","authors":"Benjamin L. Koch, Brian D. Rutter, M. Lucía Borniego, Meenu Singla-Rastogi, Dillon M. Gardner, Roger W. Innes","doi":"10.1002/jev2.70090","DOIUrl":"https://doi.org/10.1002/jev2.70090","url":null,"abstract":"<p>Extracellular vesicles (EVs) secreted by mammalian cells are highly heterogeneous in content and function. Whether this is also true for EVs secreted by plant cells is not yet known. To address this, we used high-resolution density gradient ultracentrifugation and total internal fluorescence microscopy (TIRF-M) to purify and distinguish distinct subpopulations of Arabidopsis EVs. The EV marker protein TETRASPANIN 8 (TET8) was detected specifically in medium-density EVs. TET8 and PENETRATION 1 (PEN1) were confirmed to be secreted in mostly separate EV populations using TIRF-M, while PEN1 was co-secreted with PENETRATION 3 (PEN3) much more often. Secretion of EV subpopulations marked by TET8, PEN1 and RPM1-INTERACTING PROTEIN 4 (RIN4) into the apoplast and onto the leaf surface was induced by phytohormones, changes in temperature and infection with fungal pathogens. Treatment of Arabidopsis seedlings with plant EVs delayed the progression of fungal infection by altering fungal germ tube development and fungal morphology. Significantly, extracellular RNAs, including miRNAs and siRNAs, did not co-fractionate with TET8-labeled EVs, and instead, co-fractionated with extravesicular ARGONAUTE proteins in high-density fractions. Together, these data indicate that Arabidopsis EVs are highly heterogeneous and contribute to immunity but are unlikely to mediate cross-kingdom RNA interference.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiseong Kim, Yuping Zhao, Hyun Young Kim, Sumin Kim, Yanxialei Jiang, Min Jae Lee
{"title":"Extracellular Vesicle-Mediated Delivery of 20S Proteasomes Enhances Tau Degradation in Recipient Cells","authors":"Jiseong Kim, Yuping Zhao, Hyun Young Kim, Sumin Kim, Yanxialei Jiang, Min Jae Lee","doi":"10.1002/jev2.70086","DOIUrl":"https://doi.org/10.1002/jev2.70086","url":null,"abstract":"<p>The 26S proteasome holoenzyme comprises 20S catalytic and 19S regulatory complexes. Accumulating evidence suggests that the majority of proteasomes in the extracellular space exist as free 20S proteasomes; however, their origin and pathophysiological function remain to be determined. Here, we report that cellular proteasomes are effectively packaged into the lumen of extracellular vesicles (EVs) and secreted in a structurally intact and enzymatically active 20S form. We further demonstrate that EV-encapsulated 20S proteasomes are delivered to recipient cells and facilitate the degradation of overexpressed tau proteins without disrupting global proteolytic pathways. These findings highlight a novel cell-to-cell communication system that transports the proteasomes to target cells for the clearance of proteotoxic substrates. Further characterisation of this homeostatic mechanism will improve our understanding of organismal stress response mechanisms and may provide a therapeutic approach to treat various proteinopathies, including Alzheimer's disease.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laurel A. Haines, Alex A. Baeckler, Sophi J. Schofield, Eric P. Palmer, Bradley F. Guilliams, Melinda A. Meyers, Daniel P. Regan
{"title":"Non-Specific Particle Formation During Extracellular Vesicle Labelling With the Lipophilic Membrane Dye PKH26","authors":"Laurel A. Haines, Alex A. Baeckler, Sophi J. Schofield, Eric P. Palmer, Bradley F. Guilliams, Melinda A. Meyers, Daniel P. Regan","doi":"10.1002/jev2.70079","DOIUrl":"https://doi.org/10.1002/jev2.70079","url":null,"abstract":"<p>Current approaches for the fluorescent labelling of extracellular vesicles (EVs) have been reported to produce widely variable and controversial results, highlighting a significant need for validated, reproducible labelling methods to advance the field of EV research. Lipophilic membrane dyes are commonly used but have been shown to produce non-specific fluorescent particles that are indistinguishable from labelled EVs, confounding experimental results. We aimed to distinguish conditions that can either promote or reduce the formation of non-specific dye particles when using the prototypical lipophilic membrane dye PKH26. We optimised a labelling approach that minimises the production of non-specific dye particles by altering buffer conditions during staining and validated this method across cell-based and in vivo systems of EV biodistribution. To do this, we specifically isolated small EVs using ultrafiltration and size exclusion chromatography and validated sample purity and post-isolation processing steps. We then used single-EV spectral flow cytometry and transmission electron microscopy to investigate the impact of four different buffer conditions on PKH26 non-specific particle formation. We also determined the extent to which non-specific PKH26 particles were detectable in cell-based assays and in vivo within mouse lymph nodes using flow cytometry, immunofluorescence, and intravital imaging. By optimising buffer conditions to eliminate additional protein, we were able to minimise the formation of dye aggregates while maintaining efficient EV labelling, producing a much higher signal-to-noise ratio both in vitro and in vivo. We also demonstrate that failure to include proper vehicle controls can have significant implications on experimental results, leading to false positive data. This work emphasizes the importance of adequately benchmarking EV labelling approaches as it is essential for accurate evaluation of EV trafficking in physiologic and pathologic states.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Edita Aksamitiene, Jaena Park, Marina Marjanovic, Stephen A. Boppart
{"title":"Defining Biological Variability, Analytical Precision and Quantitative Biophysiochemical Characterization of Human Urinary Extracellular Vesicles","authors":"Edita Aksamitiene, Jaena Park, Marina Marjanovic, Stephen A. Boppart","doi":"10.1002/jev2.70087","DOIUrl":"https://doi.org/10.1002/jev2.70087","url":null,"abstract":"<p>The magnitude of combined analytical errors of urinary extracellular vesicle (uEV) preparation and measurement techniques (CV<sub>A</sub>) has not been thoroughly investigated to determine whether it exceeds biological variations. We utilized technical replicates of human urine to assess the repeatability of uEV concentration and size measurements by nanoparticle tracking analysis (NTA) following differential velocity centrifugation (DC), silicon carbide, or polyethylene glycol uEV isolation methods. The DC method attained the highest precision. Consequently, DC-derived uEV size, most abundant protein levels, and optical redox ratio (ORR) were further assessed by dynamic light scattering (DLS), immunoblotting or multi-photon (SLAM) microscopy. Procedural errors primarily affected uEV counting and uEV-associated protein quantification, while instrumental errors contributed most to the total variability of NTA- and DLS-mediated uEV sizing processes. The intra-individual variability (CV<sub>I</sub>) of uEV counts assessed by NTA was smaller than inter-individual variability (CV<sub>G</sub>), resulting in an estimated index of individuality IOI < 0.6, suggesting that personalized reference interval (RI) is more suitable for interpretation of changes in subject's test results. Population-based RI was more appropriate for ORR (IOI > 1.4). The analytical performance of DC-NTA and DC-SLAM techniques met optimal CV<sub>A</sub> < 0.5 × CV<sub>I</sub> criteria, indicating their suitability for further testing in clinical laboratory settings.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Dopamine-Conjugated Extracellular Vesicles Induce Autophagy in Parkinson's Disease”","authors":"","doi":"10.1002/jev2.70082","DOIUrl":"https://doi.org/10.1002/jev2.70082","url":null,"abstract":"<p>J. H. Sul, S. Shin, H. K. Kim, et al., “Dopamine-Conjugated Extracellular Vesicles Induce Autophagy in Parkinson's Disease,” <i>Journal of Extracellular Vesicles</i> 13 (2024): e70018. https://doi.org/10.1002/jev2.70018</p><p>In the originally published article, Figure 5g contained an error. The DAPI and TH images of 6-OHDA + Dopa-EVs in Figure 5g were horizontally flipped. The corrected version of Figure 5g is provided below. This correction does not alter the description, interpretation or original conclusions of the article.</p><p></p><p>In Figure 5i, the y-axis title was missing from the graph. The correct figure is as follows:</p><p></p><p>In Materials and Methods 2.11, the dosing schedule was described differently from Figure 5a, and an extra dash was added in the title. The correct title and text are as follows:</p><p>2.11 6-OHDA-induced PD mouse model</p><p>For injection of 6-OHDA into the medial-forebrain bundle, 8- to 10-week-old C57BL/6 male mice were deeply anaesthetized using a mixture of Zoletil (30 mg/kg) (Virbac) and Rompun (10 mg/kg) (Bayer) diluted at a 1:10 ratio with saline. They were then positioned in a stereotaxic mouse frame. 6-OHDA (R&D Systems) was dissolved in 0.02% ascorbate (Sigma-Aldrich)/saline solution at a concentration of 5 mg/mL and used within 3 h. The injection was administered at a rate of 0.2 µL/min into the medial forebrain bundle at the following coordinates (relative to the bregma): anterior–posterior (A/P) = −1.2 mm, mediolateral (M/L) = −1.2 mm, and dorsal-ventral (D/V) = −4.85 mm (from the dura). After the injection, the syringe remained in place for an additional 5 min within the brain before being slowly withdrawn for a complete absorption of the solution. Control mice were injected with 0.02% ascorbic acid solution alone. To relieve mouse pain and improve survival rate after surgery, acetaminophen at a dose of 150 mg/kg was administered to mice twice a day for 3 days after injection of 6-OHDA. After discrimination of PD-induced mice using the pole-test<span>, EVs were administered intravenously (5 × 10</span><sup>8</sup> <span>particles/head) once daily for 7 consecutive days</span>, starting 3 days after 6-OHDA injection.</p><p>In Materials and Method 2.15, the antibody information listed in the manuscript was incorrect. The updated text is as follows:</p><p>… Membranes were blocked in 5% non-fat milk for 1 h at room temperature, and incubated overnight at 4°C with antibodies raised against Calnexin (AB2301, Sigma-Aldrich), TSG101 (sc-7964, Santa Cruz Biotechnology), CD9 (sc-13118, Santa Cruz Biotechnology), β-actin (A2228, AC-74, Sigma-Aldrich), CD63 (MX-49.129.5, Santa Cruz Biotechnology), tyrosine hydroxylase (2792, Cell Signaling Technology), Parkin (ab77924, clone Prk8, abcam), LC3B (NB100-2220, Novus Biologicals), NRF2 phospho (Ser40) (2073-1, Epitomics), α-synuclein (610787, clone 42/α-Synuclein, BD biosciences), Beclin-1 (A11761, ABclonal), Tubulin β3 (TUBB3) (MMS-435P, clone TUJ1, B","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ye Yuan, Hai Jiang, Rui Xue, Xiao-Jun Feng, Bi-Feng Liu, Lian Li, Bo Peng, Chen-Shuo Ren, Shi-Min Li, Na Li, Min Li, Dian-Bing Wang, Xian-En Zhang
{"title":"Identification of a Biomarker Panel in Extracellular Vesicles Derived From Non-Small Cell Lung Cancer (NSCLC) Through Proteomic Analysis and Machine Learning","authors":"Ye Yuan, Hai Jiang, Rui Xue, Xiao-Jun Feng, Bi-Feng Liu, Lian Li, Bo Peng, Chen-Shuo Ren, Shi-Min Li, Na Li, Min Li, Dian-Bing Wang, Xian-En Zhang","doi":"10.1002/jev2.70078","DOIUrl":"https://doi.org/10.1002/jev2.70078","url":null,"abstract":"<p>Antigen fingerprint profiling of tumour-derived extracellular vesicles (TDEVs) in the body fluids is a promising strategy for identifying tumour biomarkers. In this study, proteomic and immunological assays reveal significantly higher CD155 levels in plasma extracellular vesicles (EVs) from patients with non-small cell lung cancer (NSCLC) than from healthy individuals. Utilizing CD155 as a bait protein on the EV membrane, CD155+ TDEVs are enriched from NSCLC patient plasma EVs. In the discovery cohort, 281 differentially expressed proteins are identified in TDEVs of the NSCLC group compared with the healthy control group. In the verification cohort, 49 candidate biomarkers are detected using targeted proteomic analysis. Of these, a biomarker panel of seven frequently and stably detected proteins—MVP, GYS1, SERPINA3, HECTD3, SERPING1, TPM4, and APOD—demonstrates good diagnostic performance, achieving an area under the curve (AUC) of 1.0 with 100% sensitivity and specificity in receiver operating characteristic (ROC) curve analysis, and 92.3% sensitivity and 88.9% specificity in confusion matrix analysis. Western blotting results confirm upregulation trends for MVP, GYS1, SERPINA3, HECTD3, SERPING1 and APOD, and TPM4 is downregulated in EVs of NSCLC patients compared with healthy individuals. These findings highlight the potential of this biomarker panel for the clinical diagnosis of NSCLC.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 5","pages":""},"PeriodicalIF":15.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}