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Large-Scale Plasma Proteomics Reveals Preclinical Biomarkers of Incident Severe Liver Disease. 大规模血浆蛋白质组学揭示严重肝病发生的临床前生物标志物
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-09-01 DOI: 10.1002/prca.70055
Shuzhen Zhao, Chengnan Guo, Xin Zhang, Haili Wang, Yi Li, Jiayi Huang, Luojia Dai, Zhenqiu Liu, Tiejun Zhang
{"title":"Large-Scale Plasma Proteomics Reveals Preclinical Biomarkers of Incident Severe Liver Disease.","authors":"Shuzhen Zhao, Chengnan Guo, Xin Zhang, Haili Wang, Yi Li, Jiayi Huang, Luojia Dai, Zhenqiu Liu, Tiejun Zhang","doi":"10.1002/prca.70055","DOIUrl":"10.1002/prca.70055","url":null,"abstract":"<p><p>The absence of robust biomarkers for early detection of severe liver disease (SLD) highlights the critical need for high-throughput proteomics-driven discovery. In this prospective cohort study, we aimed to identify plasma protein signatures associated with incident SLD and assess their clinical utility. Using the large-scale Olink Explore 1536 platform, we quantified 1461 plasma proteins in 46951 participants from the UK Biobank community-based cohort without baseline liver disease. Over a median follow-up of 14.1 years, we identified 490 proteins significantly associated with incident SLD risk. Growth differentiation factor 15 (GDF15) emerged as the strongest predictor, achieving a C-index of 0.80 and outperforming conventional clinical indices (LiverRisk score: 0.75; FIB-4: 0.68; APRI: 0.68). Temporal trajectories revealed that GDF15 levels began increasing up to 10 years before diagnosis, with progressive elevation as the diagnosis timepoint approached. Mendelian randomization analysis supported genetic associations linking higher protein levels of GDF15, FABP1, SPON2, CHI3L1, and PIGR with SLD risk. Our large-scale proteome-wide study not only reveals significant proteomic changes preceding SLD diagnosis but also establishes GDF15 as both a promising preclinical biomarker, opening new avenues for early intervention in at-risk individuals.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 5","pages":"e70055"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Multi-Omics Landscape of Enzymatic Alterations in Systemic Lupus Erythematosus. 系统性红斑狼疮酶改变的多组学研究。
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-09-01 DOI: 10.1002/prca.70056
Lingling Zhou, Qinxin Zhang, Wei Zhang, Yong Dai
{"title":"The Multi-Omics Landscape of Enzymatic Alterations in Systemic Lupus Erythematosus.","authors":"Lingling Zhou, Qinxin Zhang, Wei Zhang, Yong Dai","doi":"10.1002/prca.70056","DOIUrl":"10.1002/prca.70056","url":null,"abstract":"<p><strong>Objective: </strong>Systemic lupus erythematosus (SLE) is an autoimmune disease closely associated with enzyme dysfunction, yet its underlying molecular mechanisms remain incompletely understood. This study aims to characterize enzyme-network alterations associated with SLE status and disease activity and to identify candidate molecules with potential clinical relevance.</p><p><strong>Methods: </strong>We integrated proteomic and phosphoproteomic data from peripheral blood mononuclear cells (PBMCs) of 130 SLE patients and 90 healthy controls (HC), along with transcriptomic data from 1461 SLE patients. Through systematic analysis of key enzyme phosphorylation sites, upstream transcription factors (TFs), and computationally prioritized candidate compounds, we sought to characterize enzyme-centered regulatory associations.</p><p><strong>Results: </strong>Integrated proteomic and phosphoproteomic analyses revealed significant metabolic and signaling pathway disturbances, along with distinct phosphorylation patterns in SLE immune cells. Multiple SLE-associated and disease-activity-associated candidate molecules were identified. Regulatory network analysis uncovered an upstream transcription factor cluster centered around STAT1. Computational drug screening identified computationally prioritized candidate compounds with multi-gene DSigDB associations, which require further clinical safety evaluation and experimental validation.</p><p><strong>Conclusions: </strong>This study constructs a molecular map of SLE, highlighting associations between enzyme-network alterations, catalytic dysregulation, and SLE-related immune molecular signatures, and identifies candidate molecules for future clinical and functional evaluation.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 5","pages":"e70056"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fecal Proteomics Suggest Potential Biomarkers for Non-Alcoholic Fatty Liver Disease and Steatohepatitis. 粪便蛋白质组学提示非酒精性脂肪性肝病和脂肪性肝炎的潜在生物标志物
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-07-01 DOI: 10.1002/prca.70047
Anna Negroni, Luisa Pieroni, Noemi Fiaschini, Francesca Palone, Mariateresa Mancuso, Roberta Vitali
{"title":"Fecal Proteomics Suggest Potential Biomarkers for Non-Alcoholic Fatty Liver Disease and Steatohepatitis.","authors":"Anna Negroni, Luisa Pieroni, Noemi Fiaschini, Francesca Palone, Mariateresa Mancuso, Roberta Vitali","doi":"10.1002/prca.70047","DOIUrl":"10.1002/prca.70047","url":null,"abstract":"<p><strong>Background and aims: </strong>Non-alcoholic Fatty Liver Disease (NAFLD) affects about a quarter of the world's population. Liver biopsy remains the gold standard for diagnosing the progressive form of NAFLD called Non-alcoholic Steatohepatitis (NASH) but it is invasive, prone to sampling errors and observer variability, and impractical for widespread use. Fecal non-invasive biomarkers have emerged as a new approach to diagnose, stage, and monitor NAFLD over time.</p><p><strong>Methods: </strong>Proteomic analysis was performed using Liquid Chromatography-Mass Spectrometry (LC-MS/MS) in fecal samples derived from mice fed with high fat and sugar diet representing NAFLD model and with the addition of 5 cycles of dextran-sulphate in drinking water to induce a NASH.</p><p><strong>Results: </strong>Qualitative and quantitative different protein profiles resulted in a comparison between the three groups of mice. An enrichment analysis of differentially expressed proteins explores the molecular pathways involved. A selection of the most significant modulated proteins between groups was performed. The proteins Transthyretin, Kallikrein1 and Trefoil Factor 3 were validated by ELISA.</p><p><strong>Conclusion: </strong>Our exploratory discovery study identified several proteins that, alone or in combination, enable a good separation between NASH, NAFLD and healthy mice, highlighting their potential as key targets for future research.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 4","pages":"e70047"},"PeriodicalIF":2.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148056482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Distinct Functional Signatures of Human Olfactory and Respiratory Mucus Revealed by Proteomics Combined With Machine Learning. 结合机器学习的蛋白质组学揭示了人类嗅觉和呼吸道粘液的独特功能特征。
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-07-01 DOI: 10.1002/prca.70049
Romain Topalian, Anna Kristina Hernandez, Karoline Lantzsch, Philipp Hubel, Chrystelle Mavoungou, Frank Rosenau, Jens Pfannstiel, Thomas Hummel, Katharina Schindowski
{"title":"Distinct Functional Signatures of Human Olfactory and Respiratory Mucus Revealed by Proteomics Combined With Machine Learning.","authors":"Romain Topalian, Anna Kristina Hernandez, Karoline Lantzsch, Philipp Hubel, Chrystelle Mavoungou, Frank Rosenau, Jens Pfannstiel, Thomas Hummel, Katharina Schindowski","doi":"10.1002/prca.70049","DOIUrl":"10.1002/prca.70049","url":null,"abstract":"<p><strong>Background: </strong>The nasal cavity includestwo distinct epithelial regions: olfactory and respiratory which fulfilldifferent roles. Despite their differences, their mucus composition, however, is yet not well elucidated.</p><p><strong>Methods: </strong>To analyze themucosal secretome, samples from the human olfactory mucus (OM) and respiratorymucus (RM) were collected in a volunteer study with 25 normosmic individualsand analyzed using label-free quantitative proteomics (LFQ), supervised machinelearning (Partial Least Squares Discriminant Analysis, PLS-DA), functionalenrichment via Gene Ontology (GO) and pathway analyses at Reactome database.</p><p><strong>Results: </strong>A total of 1,780high-confidence proteins were quantified across 50 samples. The optimizedPLS-DA model achieved robust discrimination between OM and RM (AUC = 0.93 ±0.04), identifying distinct molecular signatures. Cross-validation across GO,Reactome, and PLS-DA macro-category analyses confirmed the robustness andbiological coherence of these findings.</p><p><strong>Conclusions: </strong>Overall, this study defines twocomplementary mucosal ecosystems: a dynamic olfactory mucus optimized for highmitochondrial activity, (non-motile) ciliary renewal, and autophagy, and animmune-active respiratory mucus specialized in host defense, providing acomprehensive molecular framework of nasal regional specialization.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 4","pages":"e70049"},"PeriodicalIF":2.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An Ensemble Method for Predicting and Designing of Druggable Proteins. 可用药蛋白预测与设计的集成方法。
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-05-01 DOI: 10.1002/prca.70046
Shipra Jain, Srijanee Gupta, Gajendra P S Raghava
{"title":"An Ensemble Method for Predicting and Designing of Druggable Proteins.","authors":"Shipra Jain, Srijanee Gupta, Gajendra P S Raghava","doi":"10.1002/prca.70046","DOIUrl":"10.1002/prca.70046","url":null,"abstract":"<p><strong>Purpose: </strong>Over the years, several proteins and peptides with diverse therapeutic properties such as anticancer, antimicrobial, antihypertensive effects have been discovered. However, only a few hundred proteins are considered druggable with US FDA approval, while most of them failed during clinical trials.</p><p><strong>Experimental design: </strong>This study systematically investigates the compositional and physicochemical properties of FDA-approved proteins to develop predictive models for identifying druggable proteins. Our main dataset comprises of 356 FDA approved proteins as positive dataset and equal number of randomly selected proteins as negative dataset. We used 80% data as training set and 20% as independent validation data, with no protein in validation dataset having more than 40% similarity with any protein in training dataset.</p><p><strong>Result: </strong>Random forest-based model developed using SVC-L1 selected features obtained maximum performance AUC of 0.80 with MCC 0.61 on validation data. In addition to this, we performed MERCI-based motif analysis to find exclusive motifs/ patterns in druggable proteins. Finally, we proposed an ensemble-based method combining best performing machine learning model with exclusive motifs and achieved AUC 0.92 with MCC 0.83 on independent validation dataset.</p><p><strong>Conclusion and clinical relevance: </strong>In order to serve the scientific community, web server and standalone package of \"ThPPred\" facilitating prediction and designing of druggable proteins is proposed (https://webs.iiitd.edu.in/raghava/thppred/).</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 3","pages":"e70046"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteomic Analysis of Cervicovaginal Fluid for Diagnostic Endometriosis Biomarker Discovery. 宫颈阴道液蛋白质组学分析诊断子宫内膜异位症的生物标志物发现。
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-05-01 DOI: 10.1002/prca.70044
Emily S J Paterson, Simon Scheck, Torsten Kleffmann, Roopi Gill, Nicholas Bedford, Simon McDowell, Jane E Girling, Claire E Henry
{"title":"Proteomic Analysis of Cervicovaginal Fluid for Diagnostic Endometriosis Biomarker Discovery.","authors":"Emily S J Paterson, Simon Scheck, Torsten Kleffmann, Roopi Gill, Nicholas Bedford, Simon McDowell, Jane E Girling, Claire E Henry","doi":"10.1002/prca.70044","DOIUrl":"10.1002/prca.70044","url":null,"abstract":"<p><strong>Purpose: </strong>Endometriosis is a prevalent inflammatory condition characterised by the presence of endometrial-like tissue outside the uterus and is associated with significant challenges, including diagnostic delays and continued reliance on laparoscopy. Although extensive research has investigated potential biomarkers in various biofluids, none have been validated for clinical use.</p><p><strong>Experimental design: </strong>This pilot study explored the proteome of cervicovaginal fluid to identify biomarkers of endometriosis. SWATH-MS was performed over two experiments on cervicovaginal fluid sampled via a low vaginal swab, from people with (n = 20) and without (n = 19) surgically confirmed endometriosis. STRING, OPLS-DA modelling and ingenuity pathway analysis were used to interrogate the data. ELISA was performed validate SWATH-MS findings.</p><p><strong>Results: </strong>There were 29 proteins in experiment one and 47 proteins in experiment two identified as differentially abundant between cases and controls. No proteins were identified as differentially abundant in both experiments. Legumain (LGMN) measured via ELISA was significantly increased in the cervicovaginal fluid of people with endometriosis.</p><p><strong>Conclusions and clinical relevance: </strong>Cervicovaginal fluid proteins sampled via vaginal swab may have limited biomarker potential for endometriosis. A larger and more diverse cohort would be required to confirm the promise of cervicovaginal fluid LGMN as a candidate biomarker of endometriosis.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 3","pages":"e70044"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteome Profiles of Hypercholesterolemic Patients with and Without FH Treated with a PCSK9 Inhibitor: A Comparison of Depleted and Nondepleted Samples in a Pilot Study. 用PCSK9抑制剂治疗伴有和不伴有FH的高胆固醇血症患者的蛋白质组谱:中试研究中耗尽和未耗尽样品的比较
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-05-01 DOI: 10.1002/prca.70043
Dana Dlouha, Petr Pompach, Jana Horackova, Jaroslav Alois Hubacek, Vladimir Blaha
{"title":"Proteome Profiles of Hypercholesterolemic Patients with and Without FH Treated with a PCSK9 Inhibitor: A Comparison of Depleted and Nondepleted Samples in a Pilot Study.","authors":"Dana Dlouha, Petr Pompach, Jana Horackova, Jaroslav Alois Hubacek, Vladimir Blaha","doi":"10.1002/prca.70043","DOIUrl":"10.1002/prca.70043","url":null,"abstract":"<p><strong>Background: </strong>Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors offer a novel approach for reducing low-density lipoprotein cholesterol (LDL-C) levels in patients with familial hypercholesterolemia (FH). In our study, we aimed to compare the plasma proteome profiles of heterozygous FH (HeFH) patients and non-FH patients treated with PCSK9 inhibitors (PCSK9i).</p><p><strong>Methods: </strong>We analyzed 132 plasma samples from 38 patients. Samples were collected before the start of the PCSK9i treatment and then again at the third, sixth, and 12<sup>th</sup> months of treatment. Using LC‒MS technology, we compared two approaches: depleted and nondepleted samples.</p><p><strong>Results: </strong>Across all time points of treatment, numerous differentially expressed proteins were detected regardless of the FH status compared to baseline. We identified only three proteins with downregulated expression-PCSK9, CRTAC1, and PON1-with p<sub>adj</sub><0.05 in both the depleted and nondepleted datasets after one year of treatment. NRP1 and IGHV3-49 were differently expressed in HeFH patients compared to non-FH patients across the entire year of treatment in depleted samples (p<0.05).</p><p><strong>Conclusions: </strong>Our study suggests that there might be differences in the proteomes between individuals with HeFH and those without FH in response to PCSK9i treatment. Furthermore, PCSK9i treatment is likely to affect the plasma proteome, regardless of FH status.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 3","pages":"e70043"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteomic Analysis of Cerebrospinal Fluid from Severe COVID-19 Patients Reveals Prognostic Biomarkers Associated with Disease Outcome. 重症COVID-19患者脑脊液的蛋白质组学分析揭示了与疾病结局相关的预后生物标志物
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-03-01 DOI: 10.1002/prca.70042
Harry Alexopoulos, Martina Samiotaki, Eirini Gkogkou, Sofia Mavromati, Kleopatra Bitzogli, Georgios Panagiotou, Athanasios Tzioufas, Eleni Magira, Αnastasia Kotanidou, Ioannis Trougakos
{"title":"Proteomic Analysis of Cerebrospinal Fluid from Severe COVID-19 Patients Reveals Prognostic Biomarkers Associated with Disease Outcome.","authors":"Harry Alexopoulos, Martina Samiotaki, Eirini Gkogkou, Sofia Mavromati, Kleopatra Bitzogli, Georgios Panagiotou, Athanasios Tzioufas, Eleni Magira, Αnastasia Kotanidou, Ioannis Trougakos","doi":"10.1002/prca.70042","DOIUrl":"10.1002/prca.70042","url":null,"abstract":"<p><strong>Purpose: </strong>Coronavirus disease 2019 (COVID-19) has highlighted significant neurological complications in severe cases. Cerebrospinal fluid (CSF) proteomics could reveal biomarkers related to clinical outcome among critically ill patients.</p><p><strong>Experimental design: </strong>We performed high-resolution proteomic analyses of CSF samples from 29 intensive care unit (ICU) patients with severe COVID-19 and 19 controls. Differentially expressed proteins and associated pathways were identified through bioinformatic and statistical analyses.</p><p><strong>Results: </strong>Proteomic analysis identified 488 significantly altered proteins between COVID-19 patients and controls. Proteins linked to coagulation, inflammation, and blood-brain barrier dysfunction (e.g., SERPINC1, KNG1, PLG) were elevated in patients who survived ICU admission. Conversely, proteins associated with metabolic disruption, cellular stress, and neuroinflammation (e.g., FABP3, PDIA4) were upregulated in non-survivors. Pathway enrichment analyses confirmed involvement of immune activation, inflammatory responses, and coagulation cascades.</p><p><strong>Conclusions and clinical relevance: </strong>CSF proteomics in severe COVID-19 patients reveals potential biomarkers predictive of patient outcomes. These findings support the involvement of systemic inflammation and blood-brain barrier disruption in COVID-19 pathophysiology, suggesting novel targets for personalized intervention strategies.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 2","pages":"e70042"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Network-Based Association of IBD and Colorectal Cancer Using Proteomics Data. 基于蛋白质组学数据的IBD和结直肠癌网络关联
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-03-01 DOI: 10.1002/prca.70041
Jaiya Dhami, Swarnima Kollampallath Radhakrishnan, Dominic Russ, Sudip Mondal, Abdulrahman Alzarooni, Laura Bravo Merodio, Niharika A Duggal, Ruchi Gupta, Animesh Acharjee
{"title":"A Network-Based Association of IBD and Colorectal Cancer Using Proteomics Data.","authors":"Jaiya Dhami, Swarnima Kollampallath Radhakrishnan, Dominic Russ, Sudip Mondal, Abdulrahman Alzarooni, Laura Bravo Merodio, Niharika A Duggal, Ruchi Gupta, Animesh Acharjee","doi":"10.1002/prca.70041","DOIUrl":"10.1002/prca.70041","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a major cause of morbidity and mortality, with chronic inflammation from inflammatory bowel disease (IBD) representing a well-established risk factor. Clarifying shared molecular mechanisms may facilitate early detection and prevention strategies.</p><p><strong>Methods: </strong>Proteomic data from the UK Biobank were analysed using the Olink proximity extension assay for seven CRC-associated proteins (TFF3, TFF1, AHCY, RETN, LCN2, SELE and CEACAM5) previously identified via machine learning. Expression levels in CRC and IBD cases were compared with controls. Multilayer interaction networks, incorporating protein-protein, protein-metabolite and transcription factor-protein interactions, were generated using OmicsNet. Findings were validated in the Colonomics transcriptomic dataset.</p><p><strong>Results: </strong>All seven proteins were significantly upregulated in CRC; six (excluding CEACAM5) were also elevated in IBD. Network analysis identified AHCY and LCN2 as central hubs linking inflammatory and metabolic pathways. NF-κB and GATA2 emerged as recurrent transcriptional regulators. Colonomics validation confirmed upregulation of AHCY, LCN2 and SELE in CRC tissues.</p><p><strong>Conclusions: </strong>This multi-omics network analysis reveals a shared molecular framework between IBD and CRC, with inflammation as a key driver of colorectal carcinogenesis.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 2","pages":"e70041"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated Proteomic and Transcriptomic Analysis of Adipose Tissue-Derived Small Extracellular Vesicles in Ischemic Stroke. 缺血性卒中中脂肪组织来源的细胞外小泡的综合蛋白质组学和转录组学分析。
IF 2.9 4区 生物学
PROTEOMICS – Clinical Applications Pub Date : 2026-03-01 DOI: 10.1002/prca.70039
Zhichen Liao, Chen Sang, Wen Dong, Xiangrong Liu, Xianwei Zeng
{"title":"Integrated Proteomic and Transcriptomic Analysis of Adipose Tissue-Derived Small Extracellular Vesicles in Ischemic Stroke.","authors":"Zhichen Liao, Chen Sang, Wen Dong, Xiangrong Liu, Xianwei Zeng","doi":"10.1002/prca.70039","DOIUrl":"10.1002/prca.70039","url":null,"abstract":"<p><strong>Purpose: </strong>Ischemic stroke (IS) is a severe neurological disease with limited treatment options. Subcutaneous adipose tissue-derived small extracellular vesicles (SAT-sEVs), which are readily accessible and abundant, have emerged as promising biomarkers and therapeutic agents in various diseases. The objective of this research is to uncover the roles and regulatory mechanisms of proteins and miRNAs contained within SAT-sEVs in middle cerebral artery occlusion (MCAO) rats, aiming to discover innovative approaches and insights for IS treatment.</p><p><strong>Experimental design: </strong>To evaluate the therapeutic efficacy of SAT-sEVs, we intravenously administered them to MCAO rats and assessed neurological function and cerebral infarction 24 h after SAT-sEVs administration using behavioral scoring and TTC staining. To elucidate the potential mechanisms and ischemia-induced alterations in SAT-sEVs, we conducted integrated transcriptomic and proteomic analyses on vesicles isolated from both MCAO rats (24-h post-ischemia) and normal controls.</p><p><strong>Results: </strong>SAT-sEVs markedly alleviated neurological impairments and decreased the volume of cerebral infarcts in MCAO rats. Significant alterations were also observed in the miRNAs and proteins within SAT-sEVs following ischemic injury.</p><p><strong>Conclusions and clinical relevance: </strong>This comprehensive analysis enhances our understanding of SAT-sEVs-mediated protective mechanisms and functional alterations in IS. It establishes a solid experimental basis for the potential clinical use of SAT-sEVs in stroke rehabilitation and other related diseases.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":"20 2","pages":"e70039"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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