Journal of proteomics最新文献

{"title":"Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma","authors":"Ya-Qi Zheng ,&nbsp;Hai-Hua Huang ,&nbsp;Shu-Xian Chen ,&nbsp;Xiu-E Xu ,&nbsp;Zhi-Mao Li ,&nbsp;Yue-Hong Li ,&nbsp;Su-Zuan Chen ,&nbsp;Wen-Xiong Luo ,&nbsp;Yi Guo ,&nbsp;Wei Liu ,&nbsp;En-Min Li ,&nbsp;Li-Yan Xu","doi":"10.1016/j.jprot.2024.105233","DOIUrl":"10.1016/j.jprot.2024.105233","url":null,"abstract":"<div><p>Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction.</p></div><div><h3>Significance</h3><p>Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjugated linoleic acid (CLA) modulates bovine peripheral blood mononuclear cells (PBMC) proteome in vitro","authors":"G. Ávila ,&nbsp;F. Ceciliani ,&nbsp;D. Viala ,&nbsp;S. Dejean ,&nbsp;G. Sala ,&nbsp;C. Lecchi ,&nbsp;M. Bonnet","doi":"10.1016/j.jprot.2024.105232","DOIUrl":"10.1016/j.jprot.2024.105232","url":null,"abstract":"<div><p>Conjugated linoleic acid (CLA) is a group of natural isomers of the n-6 polyunsaturated fatty acid (PUFA) linoleic acid, exerting biological effects on cow physiology. This study assessed the impact of the mixture 50:50 (vol:vol) of CLA isomers (cis-9, trans-11 and trans-10, cis-12) on bovine peripheral blood mononuclear cells (PBMC) proteome, identifying 1608 quantifiable proteins. A supervised multivariate statistical analysis, sparse variant partial least squares – discriminant analysis (sPLS-DA) for paired data identified 407 discriminant proteins (DP), allowing the clustering between the CLA and controls. The ProteINSIDE workflow found that DP with higher abundance in the CLA group included proteins related to innate immune defenses (PLIN2, CD36, C3, C4, and AGP), with antiapoptotic (SERPINF2 and ITIH4) and antioxidant effects (HMOX1). These results demonstrated that CLA modulates the bovine PBMC proteome, supports the antiapoptotic and immunomodulatory effects observed in previous <em>in vitro</em> studies on bovine PBMC, and suggests a cytoprotective role against oxidative stress.</p></div><div><h3>Significance</h3><p>In this study, we report for the first time that the mixture 50:50 (vol:vol) of cis-9, trans-11, and trans-10, cis-12-CLA isomers modulates the bovine PBMC proteome. Our results support the immunomodulatory and antiapoptotic effects observed in bovine PBMC <em>in vitro</em>. In addition, the present study proposes a cytoprotective role of CLA mixture against oxidative stress. We suggest a molecular signature of CLA treatment based on combining a multivariate sparse discriminant analysis and a clustering method. This demonstrates the great value of sPLS-DA as an alternative option to identify discriminant proteins with relevant biological significance.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874391924001647/pdfft?md5=335f7735e285899a69bbf0c6c8a9c78f&pid=1-s2.0-S1874391924001647-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shotgun proteomics of detergent-solubilized proteins from Trypanosoma evansi","authors":"Franciane Batista ,&nbsp;Renato Simões Moreira ,&nbsp;Vilmar Benetti Filho ,&nbsp;Hércules Moura ,&nbsp;Glauber Wagner ,&nbsp;Luiz Claudio Miletti","doi":"10.1016/j.jprot.2024.105231","DOIUrl":"https://doi.org/10.1016/j.jprot.2024.105231","url":null,"abstract":"<div><p><em>Trypanosoma evansi</em>, the causative agent of surra, is the most prevalent pathogenic salivarian trypanosome and affects the majority of domesticated and wild animals in endemic regions. This work aimed to analyze detergent-solubilized <em>T. evansi</em> proteins and identify potential diagnostic biomarkers for surra. Triton X-114-extracted membrane-enriched proteins (MEP) of <em>T. evansi</em> bloodstream forms were analyzed using a gel-free technique (LC-ESI-MS/MS). 247 proteins were identified following the MS analysis of three biological and technical replicates. Two of these proteins were predicted to have a GPI-anchor, 100 (40%) were predicted to have transmembrane domains, and 166 (67%) were predicted to be membrane-bound based on at least one of six features: location (WolfPSORT, DeepLoc-2.0, Protcomp-9.0), transmembrane, GPI, and gene ontology. It was predicted that 76 (30%) of proteins had membrane evidence. Typical membrane proteins for each organelle were identified, among them ISG families (64, 65, and 75 kDa), flagellar calcium-binding protein, 24 kDa calflagin, syntaxins and oligosaccharyltransferase some of which had previously been studied in other trypanosomatids<em>. T. evansi</em> lacks singletons and exclusive orthologous groups, whereas three distinct epitopes have been identified. Data are available via ProteomeXchange with identifier <span>PXD040594</span><svg><path></path></svg>.</p></div><div><h3>Significance</h3><p><em>Trypanosoma evansi</em> is a highly prevalent parasite that induces a pathological condition known as “surra” in various species of ungulates across five continents. The infection gives rise to symptoms that are not pathognomonic, thereby posing challenges in its diagnosis and leading to substantial economic losses in the livestock industry. A significant challenge arises from the absence of a diagnostic test capable of distinguishing between <em>Trypanosoma equiperdum</em> and <em>T. evansi</em>, both of which are implicated in equine diseases. Therefore, there is a pressing need to conduct research on the biochemistry of the parasite in order to identify proteins that could potentially serve as targets for differential diagnosis or therapeutic interventions.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative proteomics of sugarcane smut fungus - Sporisorium scitamineum unravels dynamic proteomic alterations during the dimorphic transition","authors":"Nalayeni Kumaravel ,&nbsp;Leonard Barnabas Ebinezer ,&nbsp;N.M.R. Ashwin ,&nbsp;Cinzia Franchin ,&nbsp;Ilaria Battisti ,&nbsp;Paolo Carletti ,&nbsp;Amalraj Ramesh Sundar ,&nbsp;Antonio Masi ,&nbsp;Palaniyandi Malathi ,&nbsp;Rasappa Viswanathan ,&nbsp;Giorgio Arrigoni","doi":"10.1016/j.jprot.2024.105230","DOIUrl":"10.1016/j.jprot.2024.105230","url":null,"abstract":"<div><p>Life cycle of the dimorphic sugarcane smut fungi, <em>Sporisorium scitamineum</em>, involves recognition and mating of compatible saprophytic yeast-like haploid sporidia (MAT-1 and MAT-2) that upon fusion, develop into infective dikaryotic mycelia. Although the dimorphic transition is intrinsically linked with the pathogenicity and virulence of <em>S. scitamineum</em>, it has never been studied using a proteomic approach. In the present study, an iTRAQ-based comparative proteomic analysis of three distinct stages was carried out. The stages were: the dimorphic transition period - haploid sporidial stage (MAT-1 and MAT-2); the transition phase (24 h post co-culturing (hpc)) and the dikaryotic mycelial stage (48 hpc). Functional categorization of differentially abundant proteins showed that the most altered biological processes were energy production, primary metabolism, especially, carbohydrate, amino acid, fatty acid, followed by translation, post-translation and protein turnover. Several differentially abundant proteins (DAPs), especially in the dikaryotic mycelial stage were predicted as effectors. Taken together, key molecular mechanisms underpinning the dimorphic transition in <em>S. scitamineum</em> at the proteome level were highlighted. The catalogue of stage-specific and dimorphic transition-associated-proteins and potential effectors identified herein represents a list of potential candidates for defective mutant screening to elucidate their functional role in the dimorphic transition and pathogenicity in <em>S. scitamineum</em>.</p></div><div><h3>Biological significance</h3><p>Being the first comparative proteomics analysis of <em>S. scitamineum</em>, this study comprehensively examined three pivotal life cycle stages of the pathogen: the non-pathogenic haploid phase, the transition phase, and the pathogenic dikaryotic mycelial stage. While previous studies have reported the sugarcane and <em>S. scitamineum</em> interactions, this study endeavored to specifically identify the proteins responsible for pathogenicity. By analyzing the proteomic alterations between the haploid and dikaryotic mycelial phases, the study revealed significant changes in metabolic pathway-associated proteins linked to energy production, notably oxidative phosphorylation, and the citrate cycle. Furthermore, this study successfully identified key metabolic pathways that undergo reprogramming during the transition from the non-pathogenic to the pathogenic stage. The study also deciphered the underlying mechanisms driving the morphological and physiological alterations crucial for the <em>S. scitamineum</em> virulence. By studying its life cycle stages, identifying the key metabolic pathways and stage-specific proteins, it provides unprecedented insights into the pathogenicity and potential avenues for intervention. As proteomics continues to advance, such studies pave the way for a deeper understanding of plant-pathogen interactions and the development of i","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-gel protein digestion using acidic methanol produces a highly selective methylation of glutamic acid residues","authors":"Marta Lozano-Prieto ,&nbsp;Emilio Camafeita ,&nbsp;Inmaculada Jorge ,&nbsp;Andrea Laguillo-Gómez ,&nbsp;Rafael Barrero-Rodríguez ,&nbsp;Cristina A. Devesa ,&nbsp;Clara Pertusa ,&nbsp;Enrique Calvo ,&nbsp;Francisco Sánchez-Madrid ,&nbsp;Jesús Vázquez ,&nbsp;Noa B. Martin-Cofreces","doi":"10.1016/j.jprot.2024.105229","DOIUrl":"10.1016/j.jprot.2024.105229","url":null,"abstract":"<div><p>Mass-tolerant open search methods allow the high-throughput analysis of modified peptides by mass spectrometry. These techniques have paved the way to unbiased analysis of post-translational modifications in biological contexts, as well as of chemical modifications produced during the manipulation of protein samples. In this work, we have analyzed in-depth a wide variety of samples of different biological origin, including cells, extracellular vesicles, secretomes, centrosomes and tissue preparations, using Comet-ReCom, a recently improved version of the open search engine Comet-PTM. Our results demonstrate that glutamic acid residues undergo intensive methyl esterification when protein digestion is performed using in-gel techniques, but not using gel-free approaches. This effect was highly specific to Glu and was not found for other methylable residues such as Asp.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-MS/MS profiling and analysis of Bacillus licheniformis extracellular proteins for antifungal potential against Candida albicans","authors":"Jyoti Sankar Prusty,&nbsp;Awanish Kumar","doi":"10.1016/j.jprot.2024.105228","DOIUrl":"10.1016/j.jprot.2024.105228","url":null,"abstract":"<div><p><em>Candida albicans</em>, a significant human pathogenic fungus, employs hydrolytic proteases for host invasion. Conventional antifungal agents are reported with resistance issues from around the world. This study investigates the role of <em>Bacillus licheniformis</em> extracellular proteins (ECP) as effective antifungal peptides (AFPs). The aim was to identify and characterize the ECP of <em>B. licheniformis</em> through LC-MS/MS and bioinformatics analysis. LC-MS/MS analysis identified 326 proteins with 69 putative ECP, further analyzed <em>in silico</em>. Of these, 21 peptides exhibited antifungal properties revealed by classAMP tool and are predominantly anionic. Peptide-protein docking revealed interactions between AFPs like Peptide chain release factor 1 (Q65DV1_Seq1: SASEQLSDAK) and Putative carboxy peptidase (Q65IF0_Seq7: SDSSLEDQDFILESK) with <em>C. albicans</em> virulent SAP5 proteins (PDB ID <span>2QZX</span><svg><path></path></svg>), forming hydrogen bonds and significant Pi-Pi interactions. The identification of <em>B. licheniformis</em> ECP is the novelty of the study that sheds light on their antifungal potential. The identified AFPs, particularly those interacting with bonafide pharmaceutical targets SAP5 of <em>C. albicans</em> represent promising avenues for the development of antifungal treatments with AFPs that could be the pursuit of a novel therapeutic strategy against <em>C. albicans</em>.</p></div><div><h3>Significance of study</h3><p>The purpose of this work was to carry out proteomic profiling of the secretome of <em>B. licheniformis</em>. Previously, the efficacy of <em>Bacillus licheniformis</em> extracellular proteins against <em>Candida albicans</em> was investigated and documented in a recently communicated manuscript, showcasing the antifungal activity of these proteins. In order to achieve high-throughput identification of ES (Excretory-secretory) proteins, the utilization of liquid chromatography tandem mass spectrometry (LC-MS) was utilized. There was a lack of comprehensive research on AFPs in <em>B. licheniformis</em>, nevertheless. The proteins secreted by <em>B. licheniformis</em> in liquid medium were initially discovered using liquid chromatography-tandem mass spectrometry (LC-MS) analysis and identification in order to immediately characterize the unidentified active metabolites in fermentation broth.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology combined with metabolomics to reveal the anti-fibrotic mechanism of Polygoni Orientalis Fructus in CCl4-induced hepatic fibrosis rats","authors":"Lizhou Ma ,&nbsp;Yu Chen ,&nbsp;Rong Yue ,&nbsp;Ziyu Li ,&nbsp;Yibo Wang ,&nbsp;Yanggang Bian ,&nbsp;Miao Wang","doi":"10.1016/j.jprot.2024.105227","DOIUrl":"10.1016/j.jprot.2024.105227","url":null,"abstract":"<div><p>Polygoni Orientalis Fructus (POF), a dried ripe fruit of <em>Polygonum orientale</em> L., is commonly used in China for liver disease treatment. However, its therapeutic mechanism remains unclear. The aim of this study was to elucidate the effects of POF on the regulation of endogenous metabolites and identify its key therapeutic targets in hepatic fibrosis (HF) rats by integrating network pharmacology and metabolomics approaches. First, serum liver indices and histopathological analyses were used to evaluate the therapeutic effects of POF on carbon tetrachloride (CCl₄)-induced HF. Subsequently, differential metabolites and potential therapeutic targets of POF were screened using plasma metabolomics and network pharmacology, respectively. The key targets of POF were identified by overlapping differential metabolite-associated targets with the potential targets and validated by molecular docking and ELISA experiments. The results showed that POF effectively alleviated HF in rats. A total of 51 metabolites related to HF were screened, and 24 were associated with POF. 232 potential therapeutic targets were identified by network pharmacology analysis. Finally, six key targets were identified through a combined analysis. Furthermore, molecular docking and ELISA validation revealed that AGXT, PAH, and NOS3 are targets of POF action, while CBS, ALDH2, and ARG1 were identified as potential targets.</p></div><div><h3>Significance</h3><p>POF is now commonly used in the treatment of liver disease, but its mechanism of action remains unclear. Current studies on metabolomics of liver disease primarily focuse on the interpretation of differential metabolites and related metabolic pathways. This research delves into the intricate details of metabolomics findings via network pharmacology to uncover the targets and pathways of drug action.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative proteome analysis of bone marrow interstitial fluid and serum reveals candidate signature for acute myeloid leukemia","authors":"Saikiran Jajula ,&nbsp;Venkateshwarlu Naik ,&nbsp;Bhargab Kalita ,&nbsp;Uday Yanamandra ,&nbsp;Sanjeevan Sharma ,&nbsp;Tathagat Chatterjee ,&nbsp;Sadananad Bhanuse ,&nbsp;Praneeta Pradip Bhavsar ,&nbsp;Khushman Taunk ,&nbsp;Srikanth Rapole","doi":"10.1016/j.jprot.2024.105224","DOIUrl":"10.1016/j.jprot.2024.105224","url":null,"abstract":"<div><p>Acute myeloid leukemia (AML) is an aggressive form of blood cancer and clinically highly heterogeneous characterized by the accumulation of clonally proliferative immature precursors of myeloid lineage leading to bone marrow failure. Although, the current diagnostic methods for AML consist of cytogenetic and molecular assessment, there is a need for new markers that can serve as useful candidates in diagnosis, prognosis and understanding the pathophysiology of the disease. This study involves the investigation of alterations in the bone marrow interstitial fluid and serum proteome of AML patients compared to controls using label-free quantitative proteomic approach. A total of 201 differentially abundant proteins were identified in AML BMIF, while in the case of serum 123 differentially abundant proteins were identified. The bioinformatics analysis performed using IPA revealed several altered pathways including FAK signalling, IL-12 signalling and production of macrophages etc. Verification experiments were performed in a fresh independent cohort of samples using MRM assays led to the identification of a panel of three proteins viz., PPBP, APOH, ENOA which were further validated in a new cohort of serum samples by ELISA. The three-protein panel could be helpful in the diagnosis, prognosis and understanding of the pathophysiology of AML in the future.</p></div><div><h3>Biological Significance</h3><p>Acute Myeloid Leukemia (AML) is a type haematological malignancy which constitute one third of total leukemias and it is the most common acute leukemia in adults. In the current clinical practice, the evaluation of diagnosis and progression of AML is largely based on morphologic, immunophenotypic, cytogenetic and molecular assessment. There is a need for new markers/signatures which can serve as useful candidates in diagnosis and prognosis. The present study aims to identify and validate candidate biosignature for AML which can be useful in diagnosis, prognosis and understand the pathophysiology of the disease. Here, we identified 201 altered proteins in AML BMIF and 123 in serum. Among these altered proteins, a set of three proteins viz., pro-platelet basic protein (CXCL7), enolase 1 (ENO1) and beta-2-glycoprotein 1 (APOH) were significantly increased in AML BMIF and serum suggest that this panel of proteins could help in future AML disease management and thereby improving the survival expectancy of AML patients.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep analysis of total serum N-glycome suggests glyco-signatures for phospholipase A2 receptor 1-related idiopathic membranous nephropathy diagnosis","authors":"Yan Cai ,&nbsp;Weifu Ren ,&nbsp;Siqian Li ,&nbsp;Rijing Liao ,&nbsp;Qi Bian","doi":"10.1016/j.jprot.2024.105223","DOIUrl":"10.1016/j.jprot.2024.105223","url":null,"abstract":"<div><p>Idiopathic membranous nephropathy (IMN) is an antibody-mediated and kidney-specific autoimmune disease, with the antigen phospholipase A2 receptor 1 (PLA2R1) accounting for approximately 70% of IMN cases. Although a variety of new podocyte target antigens and their autoantibodies have been identified, they are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. N-glycans play vital roles in renal system and their pathobiological relevance has become increasingly recognized in many kidney diseases, but not fully explored in IMN. To find possible glyco-signatures for PLA2R1-related IMN diagnosis, we herein established a comprehensive workflow for total serum N-glycome analysis based on our recently developed mass spectrometry (MS)-based N-glycan purification method, named Ultrafast Glycoprotein Immobilization for Glycan extraction (UltraGIG). A total of 191 N-glycans were identified from IMN patients, representing the largest N-glycome dataset in IMN. Compared to healthy controls, up-regulation of sialylation and core-fucosylation as well as down-regulation of galactosylation were observed in PLA2R1-positive IMN patients, and up-regulation of hyper-galactosylation was specific for PLA2R1-negative IMN patients. A six-glycan marker panel consisting of H4N3S1, H4N3F1, H6N4S2, H6H5F1S2, H6N5 and H6N6F1S1, was proposed to aid in the accurate diagnosis of PLA2R1-related IMN, which provided new insights into IMN biomarker study.</p></div><div><h3>Significance</h3><p>PLA2R1-related IMN is a kidney-specific autoimmune disease with a high risk of developing end-stage renal disease (ESRD) and even kidney failure. Current biomarkers are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. An in-depth MS analysis of total serum N-glycome of PLA2R1-related IMN patients was conducted for the first time. We generated the largest dataset of serum N-glycome for IMN to date, and proposed a novel six-glycan marker panel that may help the accurate diagnosis of PLA2R1-related IMN.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteomics analysis reveals potential biomarkers for intracranial aneurysm formation and rupture","authors":"Chenchen Wang,&nbsp;Yuwei Han,&nbsp;Xiaoming Li","doi":"10.1016/j.jprot.2024.105216","DOIUrl":"10.1016/j.jprot.2024.105216","url":null,"abstract":"<div><p>The aim of this study was to investigate the plasma proteome in individuals with intracranial aneurysms (IAs) and identify biomarkers associated with the formation and rupture of IAs. Proteomic profiles (<em>N</em> = 1069 proteins) were assayed in plasma (<em>N</em> = 120) collected from patients with ruptured and unruptured intracranial aneurysms (RIA and UIA), traumatic subarachnoid hemorrhage (tSAH), and healthy controls (HC) using tandem mass tag (TMT) labeling quantitative proteomics analysis. Gene ontology (GO) and pathway analysis revealed that these relevant proteins were involved in immune response and extracellular matrix organization pathways. Seven candidate biomarkers were verified by ELISA in a completely separate cohort for validation (<em>N</em> = 90). Among them, FN1, PON1, and SERPINA1 can be utilized as diagnosis biomarkers of IA, with a combined area under the ROC curve of 0.891. The sensitivity was 93.33%, specificity was 75.86%, and accuracy was 87.64%. PFN1, ApoA-1, and SERPINA1 can serve as independent risk factors for predicting aneurysm rupture. The combined prediction of aneurysm rupture yielded an area under the ROC curve of 0.954 with a sensitivity of 96.15%, specificity of 81.48%, and accuracy of 88.68%. This prediction model was more effective than PHASES score. In conclusion, high-throughput proteomics analysis with population validation was performed to assess blood-based protein expression characteristics. This revealed the potential mechanism of IA formation and rupture, facilitating the discovery of biomarkers.</p></div><div><h3>Significance</h3><p>Although the annual rupture rate of small unruptured aneurysms is believed to be minimal, studies have indicated that ruptured aneurysms typically have an average size of 6.28 mm, with 71.8% of them being &lt;7 mm in diameter. Hence, evaluating the possibility of rupture in UIA and making a choice between aggressive treatment and conservative observation emerges as a significant challenge in the management of UIA. No biomarker or scoring system has been able to satisfactorily address this issue to date. It would be significant to develop biomarkers that could be used for early diagnosis of IA as well as for prediction of IA rupture. After TMT proteomics analysis and ELISA validation in independent populations, we found that FN1, PON1, and SERPINA1 can be utilized as diagnostic biomarkers for IA, and PFN1, ApoA-1, and SERPINA1 can serve as independent risk factors for predicting aneurysm rupture. Especially, when combined with ApoA-1, SERPINA1, and PFN1 for predicting IA rupture, the area under the curve (AUC) was 0.954 with a sensitivity of 96.15%, specificity of 81.48%, and accuracy of 88.68%. This prediction model was more effective than PHASES score.</p></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}