Journal of Proteome Research最新文献_第2页

Salivary Glycoprofiling via a Machine Learning-Augmented Lectin Microarray for Noninvasive Risk Stratification of Lung Cancer 通过机器学习增强凝集素微阵列进行无创肺癌风险分层的唾液糖谱分析

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-09-15 DOI: 10.1021/acs.jproteome.6c00376

Fan Zhang, Zhen Tang, Haoqi Du, Biyue Ma, Xia Liu, Ziyi Chang, Zeyu Zhao, Xinyu Zhang, Jinying Wang, Changchang Zhang, Boyu Wei, Jian Shu, Chen Zhang, Mingwei Chen, Hailong Xie, Zheng Li

{"title":"Salivary Glycoprofiling via a Machine Learning-Augmented Lectin Microarray for Noninvasive Risk Stratification of Lung Cancer","authors":"Fan Zhang, Zhen Tang, Haoqi Du, Biyue Ma, Xia Liu, Ziyi Chang, Zeyu Zhao, Xinyu Zhang, Jinying Wang, Changchang Zhang, Boyu Wei, Jian Shu, Chen Zhang, Mingwei Chen, Hailong Xie, Zheng Li","doi":"10.1021/acs.jproteome.6c00376","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00376","url":null,"abstract":"Although aberrant glycosylation is closely associatedwith lungcancer (LC), salivary glycopatterns and their discriminatory valueacross healthy individuals, benign pulmonary disease, and LC remaininsufficiently characterized. We profiled saliva from 307 participantsusing a lectin microarray, comprising a development cohort of 227participants and an independent test cohort of 80 participants. Fivetask-specific LASSO-logistic regression models were constructed todistinguish pulmonary disease, LC, and LC subtypes. A separate Nom-LCmodel combined consensus lectin features selected by LASSO and supportvector machine recursive feature elimination with clinical variables.Salivary glycopatterns differed among healthy volunteers, benign pulmonarydisease, and LC groups, and the five task-specific models showed discriminatoryperformance across pulmonary disease, LC, and exploratory subtypeclassification tasks. The resulting Nom-LC model incorporated smokinghistory and four lectin signals (HHL, PNA, RCA120, and PWM), yieldingAUCs of 0.908 and 0.907 in the training and internal validation sets.In the independent test cohort, the AUC was 0.903 (95% CI, 0.831–0.976);at the prespecified cutoff, sensitivity, specificity, and accuracywere 86.36%, 94.44%, and 90.00%, respectively. These findings supportfurther evaluation of salivary glycopatterns as an auxiliary toolfor LC risk stratification, but prospective multicenter validationis required.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5391–5403"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093628","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}

引用次数: 0

Novel Relationships between the ICAD, CD53, GRM1, and GSTmu Protein Levels and Atherosclerosis and Cardiovascular Outcomes ICAD、CD53、GRM1和GSTmu蛋白水平与动脉粥样硬化和心血管结局之间的新关系

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-09-21 DOI: 10.1021/acs.jproteome.5c00843

Nadezhda G. Gumanova, Alexander A. Mols, Anna R. Levshina, Maria A. Khadorich, Elena S. Luboyatnikova, Artem S. Shanoyan, Natalya L. Bogdanova, Dmitry K. Vasilyev, Anton R. Kiselev

{"title":"Novel Relationships between the ICAD, CD53, GRM1, and GSTmu Protein Levels and Atherosclerosis and Cardiovascular Outcomes","authors":"Nadezhda G. Gumanova, Alexander A. Mols, Anna R. Levshina, Maria A. Khadorich, Elena S. Luboyatnikova, Artem S. Shanoyan, Natalya L. Bogdanova, Dmitry K. Vasilyev, Anton R. Kiselev","doi":"10.1021/acs.jproteome.5c00843","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00843","url":null,"abstract":"Theaim of the present study was to identify serum proteins associatedwith atherosclerosis and its comorbidities. The 3-year follow-up included216 patients subjected to coronary angiography. Gensini score wasused to quantify coronary atherosclerosis, and peripheral atherosclerosiswas assessed by B-mode ultrasound. Serum proteins were profiled usingan Explorer antibody microarray (Full Moon Biosystems, USA). In-houseELISA or commercial ELISA kits were used to validate the microarraydata in the total cohort for the top five proteins from the atheroscleroticprofile. Only ICAD (DNA fragmentation factor subunit, DFF45/ICAD)was linked to type 2 diabetes and the presence of coronary arterystenosis regardless of the severity of stenosis. CD53 was also associatedwith coronary stenosis. IL-6 was associated with diabetes, and GSTmu(glutathione S-transferase Mu3) was associated with brachiocephalicstenosis ≥ 60% and with femoral and coronary arterial lesions.Only GRM1 (glutamate metabotropic receptor 1) showed inverse associationswith coronary stenosis and cardiovascular outcomes (r = −0.24and P = 0.025 and r = −0.31 and P = 0.007, respectively). Moreover,GRM1 was inversely associated with femoral lesions ≥ 30%. Thus,we identified previously unreported associations of the ICAD, CD53,GRM1, and GSTmu proteins with atherosclerosis, diabetes, and nonfatalcardiovascular outcomes.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5039–5048"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100844","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}

引用次数: 0

High-Throughput Targeted Paleoproteomics Sex Estimation on Medieval Great Moravian Individuals Using MALDI-CASI-FTICR Mass Spectrometry MALDI-CASI-FTICR质谱法对中世纪大摩拉维亚人的高通量靶向古蛋白质组学性别估计

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-08-28 DOI: 10.1021/acs.jproteome.6c00163

Fabrice Bray, Anežka Pilmann Kotěrová, Lisa Garbé, Marc Haegelin, Benoît Bertrand, Kevimy Agossa, Christian Rolando, Petr Velemínský, Jaroslav Brůžek, Marine Morvan

{"title":"High-Throughput Targeted Paleoproteomics Sex Estimation on Medieval Great Moravian Individuals Using MALDI-CASI-FTICR Mass Spectrometry","authors":"Fabrice Bray, Anežka Pilmann Kotěrová, Lisa Garbé, Marc Haegelin, Benoît Bertrand, Kevimy Agossa, Christian Rolando, Petr Velemínský, Jaroslav Brůžek, Marine Morvan","doi":"10.1021/acs.jproteome.6c00163","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00163","url":null,"abstract":"The estimation of the biological sex of archeologicalremains iscrucial information in bioarcheology and forensic anthropology. Inrecent years, proteomics based on molecular sexual dimorphism hasemerged as a preferred method, particularly because of its minimallyinvasive approach for extracting amelogenin X and Y proteins fromtooth enamel. However, there is an increasing demand to acceleratethis process and facilitate the analysis of large archeological assemblages.This study presents a novel high-throughput targeted paleoproteomicsmethod for biological sex estimation using MALDI-CASI-FTICR mass spectrometry.This approach combines the strengths of existing methods, includingultrahigh resolution, significantly reduced processing times, targetedanalysis, and scalability to large archeological sample sets. Themethod was initially validated on modern individuals with known sexand subsequently applied to 130 adult and juvenile individuals frommedieval Great Moravia (present-day Czech Republic). Biological sexwas successfully estimated for all but one of the individuals. Theresults not only provide a more efficient biological sex estimationbut also help to resolve a few errors in sex assessment previouslyencountered with osteomorphological and tooth morphometric techniques.The implementation of this method significantly improves the accuracyand efficiency of biological sex estimation, offering a powerful toolfor anthropological research.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5173–5188"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093575","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}

引用次数: 0

Ontogenetic Variation in Composition and Bioactivity of Common Adder (Vipera berus) Venom Revealed by Genome-Guided Proteomics and In Vitro Functional Assays 基因组引导蛋白质组学和体外功能分析揭示了蝰蛇毒液组成和生物活性的个体发生变异

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-08-31 DOI: 10.1021/acs.jproteome.6c00042

Lennart Schulte, Johanna Eichberg, Alfredo Cabrera-Orefice, Harry Wölfel, Paul Hien, Maik Damm, Tilman Schell, Charlotte Gerheim, Alexander Ben Hamadou, Sabine Hurka, Thomas Lindner, Gregor Geisler, Ignazio Avella, Kornelia Hardes, Carola Greve, Tim Lüddecke

{"title":"Ontogenetic Variation in Composition and Bioactivity of Common Adder (Vipera berus) Venom Revealed by Genome-Guided Proteomics and In Vitro Functional Assays","authors":"Lennart Schulte, Johanna Eichberg, Alfredo Cabrera-Orefice, Harry Wölfel, Paul Hien, Maik Damm, Tilman Schell, Charlotte Gerheim, Alexander Ben Hamadou, Sabine Hurka, Thomas Lindner, Gregor Geisler, Ignazio Avella, Kornelia Hardes, Carola Greve, Tim Lüddecke","doi":"10.1021/acs.jproteome.6c00042","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00042","url":null,"abstract":"Ontogenetic shifts in diet are well documented in snakesand areincreasingly linked to age-related venom variation. The common adder, Vipera berus, exhibits a dietary transition from predominantlyectothermic prey in its early life to increasingly incorporating endothermicprey as an adult. Here, we investigate whether this dietary shiftis reflected in age-related changes in the venom composition and bioactivityof V. berus. Venoms from captive-bred V. berus from Germany were obtained and pooled across five agegroups, from neonates to adults. Venom profiles were assessed by SDS-PAGEand genome-guided shotgun proteomics, with quantification based onnormalized spectral abundance factors (NSAF) using a toxin-gene cataloguegenerated from a novel V. berus genome assembly.In parallel, we assayed general protease and PLA2 activities,as well as FXa-, thrombin-, and plasmin-like activities, and cytotoxicitytoward mammalian cell lines. We identified two distinct age-relatedvenom phenotypes (ontotypes): an svMP/CTL-rich ontotype A (≤1year) and an svSP/PLA2-rich ontotype B (≥2 years).Functionally, protease activity decreased with age, whereas thrombin-like,plasmin-like and PLA2 activities, and cytotoxicity, increased.Our findings indicate an ontogenetic shift in composition and activitiesof V. berus venom that parallels dietary transitionsand potentially reflect adaptation to differing prey physiologies.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5103–5113"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093561","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}

引用次数: 0

Pan-Cancer Metabolic Landscapes: A Multiomics View 泛癌症代谢景观：多组学观点

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-08-27 DOI: 10.1021/acs.jproteome.6c00346

Yiguang Bai, Qiaoling Chen, Yuan Li

{"title":"Pan-Cancer Metabolic Landscapes: A Multiomics View","authors":"Yiguang Bai, Qiaoling Chen, Yuan Li","doi":"10.1021/acs.jproteome.6c00346","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00346","url":null,"abstract":"Metabolic reprogramming fuels cancer progression, butwhether commonmetabolic patterns exist across diverse malignancies remains incompletelyunderstood. To address this, we integrated large-scale proteomic,transcriptomic [The Cancer Genome Atlas (TCGA)], and spatial transcriptomic(Spatial Meta-Transcriptome Database) data sets comprising 3226 samplesacross 24 human cancer types. Utilizing a highly controlled, predominantlypatient-matched design to minimize background noise, we characterizedthe pan-cancer metabolic landscape via reaction-level functional taskscoring, pathway enrichment, multiomics integration, network modeling,survival analysis, and microenvironmental coupling. Consistently upregulatedglycan biosynthesis pathways─particularly fucosylation andsialylation─and broadly enhanced nucleotide metabolism highlightedconserved programs potentially associated with tumor growth, adaptation,and immune evasion. These signatures proved robust against variationsin tumor purity across the TCGA cohorts. Furthermore, gene coexpressionnetwork modeling prioritized specific hub genes associated with thispan-cancer restructuring. Exploratory high-resolution mapping alignedtumor immunogenicity with specific glycan pathways. Notably, tumor-intrinsicglycan upregulation negatively correlates with their immune scorealignment, suggesting that tumor hyperactivation may obscure immunesignals in bulk tissue. Together, our results define a robust computationallandscape of shared metabolic alterations, providing a data-drivenframework to guide future experimental validation of candidate therapeutictargets across diverse oncological contexts.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5328–5338"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093584","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}

引用次数: 0

A Robust DIA-Based Platform for Large-Scale Plasma Glycoproteomics and Biomarker Discovery 一个强大的基于dia的大规模血浆糖蛋白组学和生物标志物发现平台

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-09-18 DOI: 10.1021/acs.jproteome.6c00522

Chi-Hung Lin, Sayee Sawale, Mark Marispini, Adam Poltorak, Joon-Yong Lee, Natalie Smith, Wan-Fang Chou, Hao Qian, Philip Ma, Bruce Wilcox

{"title":"A Robust DIA-Based Platform for Large-Scale Plasma Glycoproteomics and Biomarker Discovery","authors":"Chi-Hung Lin, Sayee Sawale, Mark Marispini, Adam Poltorak, Joon-Yong Lee, Natalie Smith, Wan-Fang Chou, Hao Qian, Philip Ma, Bruce Wilcox","doi":"10.1021/acs.jproteome.6c00522","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00522","url":null,"abstract":"Structural changes in protein glycosylation are recognizedas phenotypesin numerous diseases, including cancer. Despite the promise of glycoproteomicsfor diagnostic biomarker discovery, large-scale studies remain limitedby challenges in reproducibility, throughput, and quantitative precision.Here, we present a robust data-independent acquisition (DIA)-basedplasma glycoproteomics platform that enables high-throughput and reproducibleglycopeptide quantification suitable for large-cohort studies. Theworkflow integrates automated in-solution digestion and enrichment,optimized DIA-LC-MS acquisition, and a customized bioinformatics pipelineto achieve reproducible glycopeptide identification and quantitation.Across 560 replicates of a pooled human plasma sample processed inseven batches, the platform achieved high reproducibility, with intra-batchcoefficients of variation (CVs) below 15% (n = 80 per batch) and aninter-batch CV of 22.9%. The method accurately captured expected foldchanges from spiked-in glycoprotein standards. In the setting of aproof-of-concept pilot study to demonstrate the platform’sability to detect disease-associated glycosylation differences, theplatform successfully identified glycoform-specific changes and distinguishedbetween noncancer individuals (n = 39) and those with stage III/IVlung cancer (n = 39). Together, these results establish a high-throughputDIA-based glycoproteomics workflow suitable for large-cohort studiesto discover glycopeptide biomarker candidates.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5523–5533"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093611","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}

引用次数: 0

Prioritizing Peptides for Targeted Mass Spectrometry Experiments Using Deep Learning 利用深度学习为靶向质谱实验确定肽的优先级

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-09-20 DOI: 10.1021/acs.jproteome.6c00457

Shreyash Sonthalia, Bo Wen, Priank Dasgupta, Chris Hsu, Michael J. MacCoss, William Stafford Noble

{"title":"Prioritizing Peptides for Targeted Mass Spectrometry Experiments Using Deep Learning","authors":"Shreyash Sonthalia, Bo Wen, Priank Dasgupta, Chris Hsu, Michael J. MacCoss, William Stafford Noble","doi":"10.1021/acs.jproteome.6c00457","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00457","url":null,"abstract":"One critical step in any targeted mass spectrometry experimentis selecting, from each protein of interest, a small number of peptidesthat respond well in the mass spectrometer and can serve as reliableproxies for protein quantification. Existing methods select targetpeptides either by relying on prior empirical measurements, limitingtheir applicability to previously observed peptides, or using machinelearning to predict peptide behavior from sequence alone. However,current machine learning tools suffer from various limitations, includingusing detectability as an indirect proxy for intensity, relying onsmall training sets, or ignoring the precursor charge state. In thisstudy, we introduce Bromo, a transformer-based deep learning modelthat ranks peptide precursors from a given protein by their relativeresponse, taking charge state into account. Trained on millions ofannotated peptide pairs derived from large-scale, publicly availabledata-independent acquisition mass spectrometry data, Bromo consistentlyoutperforms existing sequence-based methods across diverse, independentdata sets. Furthermore, we show that fine-tuning Bromo on experiment-specificdata can account for differences in sample preparation, sample matrix,and instrument platform, all of which influence which peptides serveas optimal targets. This adaptability makes Bromo a practical toolfor selecting target peptides for selected reaction monitoring andparallel reaction monitoring assay development across a wide rangeof experimental conditions.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5469–5479"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124667","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}

引用次数: 0

A Novel Approach for Generating Antigen Interference-Free Antipeptide Polyclonal Antibodies for Quantitative Measurements of Low-Abundance Protein Biomarkers Using Ultrasensitive Antipeptide Immunocapture LC–MS/MS Assays 使用超灵敏的抗多肽免疫捕获LC-MS /MS测定方法产生无抗原干扰的抗多肽多克隆抗体，用于定量测量低丰度蛋白质生物标志物

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-08-30 DOI: 10.1021/acs.jproteome.6c00171

Huidong Gu, Sagar Kawle, Suresh Venkateswaran, Ana Liliac Zajontz, Jianing Zeng, Graham Yearwood, Lina Luo, Jim X. Shen

{"title":"A Novel Approach for Generating Antigen Interference-Free Antipeptide Polyclonal Antibodies for Quantitative Measurements of Low-Abundance Protein Biomarkers Using Ultrasensitive Antipeptide Immunocapture LC–MS/MS Assays","authors":"Huidong Gu, Sagar Kawle, Suresh Venkateswaran, Ana Liliac Zajontz, Jianing Zeng, Graham Yearwood, Lina Luo, Jim X. Shen","doi":"10.1021/acs.jproteome.6c00171","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00171","url":null,"abstract":"Antigen interference from residual antigen peptides isa persistentchallenge in antipeptide immunocapture liquid chromatography–tandemmass spectrometry (IC-LC–MS/MS) assays, particularly when quantifyinglow-abundance protein biomarkers. Traditionally, carrier protein-conjugatedsurrogate peptides identical to those used in LC–MS/MS quantificationare employed as antigens for immunization, often resulting in varyingdegrees of antigen interference from the resulting antipeptide polyclonalantibodies (pAbs). While precapture purification and other mitigationstrategies can reduce interference, they may be insufficient for ultrasensitiveantipeptide IC-LC–MS/MS assays. Here, for the first time, wedemonstrate the use of carrier-protein-conjugated, stable isotopicallylabeled surrogate peptides as antigens for immunization. This strategyensures that residual antigen peptide is distinguishable from endogenousanalytes by mass spectrometry, effectively eliminating antigen interference.This paper details the design principles for stable isotopically labeledsurrogate peptides used in antigen preparation and compares the performanceof pAbs generated using labeled versus traditional nonlabeled peptideantigens. Results from over 20 batches of antipeptide pAbs demonstratethat this method enables the routine generation of antigen interference-freeantipeptide pAbs, facilitating the development of ultrasensitive antipeptideIC-LC–MS/MS assays for low-abundance protein biomarker quantificationwithout incurring additional time and significant cost. Data are availablevia ProteomeXchange with an identifier of PXD076272.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5246–5254"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124827","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}

引用次数: 0

Integrated Multi-Omics Analysis Reveals Candidate Serum Biomarkers Linked to Cancer-Associated Fibroblast-Mediated Extracellular Matrix Remodeling in Metastatic Gastric Cancer 综合多组学分析揭示了转移性胃癌中与癌症相关成纤维细胞介导的细胞外基质重塑相关的候选血清生物标志物

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-09-14 DOI: 10.1021/acs.jproteome.6c00601

Kewei Du, Shan Gao, Haichen Wang, Wenfei Hu, Zejing Liu, Caiyan Gao, Linmei Chen, Tuanjie Che, Linjing Li, Shangdi Zhang

{"title":"Integrated Multi-Omics Analysis Reveals Candidate Serum Biomarkers Linked to Cancer-Associated Fibroblast-Mediated Extracellular Matrix Remodeling in Metastatic Gastric Cancer","authors":"Kewei Du, Shan Gao, Haichen Wang, Wenfei Hu, Zejing Liu, Caiyan Gao, Linmei Chen, Tuanjie Che, Linjing Li, Shangdi Zhang","doi":"10.1021/acs.jproteome.6c00601","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00601","url":null,"abstract":"Metastatic gastric cancer remainsa major cause of cancer-relatedmortality, while currently available serum biomarkers have limitedperformance for metastatic risk assessment. This study aimed to identifycandidate serum biomarkers associated with gastric cancer progressionthrough quantitative proteomics and integrated multi-omics analysis.Serum data-independent acquisition (DIA) proteomics was performedin patients with metastatic gastric cancer and healthy controls, followedby integration with TCGA-STAD survival analysis and multi-algorithmmachine-learning modelling to identify clinically relevant candidates.Single-cell RNA sequencing, spatial transcriptomics, and cell–cellcommunication analyses were further applied to characterize the tumormicroenvironmental context of candidate genes. Serum ITIH3 levelswere validated by ELISA in healthy controls, non-metastatic gastriccancer, lymph-node-only metastatic gastric cancer, and distant metastaticgastric cancer groups. Proteomic analysis identified 45 differentiallyexpressed proteins, and ITIH3, VWF, SH3BGRL3, and PKLR were prioritizedthrough integrated analyses. Single-cell analyses indicated that ITIH3expression was mainly associated with cancer-associated fibroblast-relatedextracellular matrix remodeling signatures. ELISA validation demonstratedprogressively increased serum ITIH3 levels during gastric cancer progression,with favorable discrimination among selected disease groups. Thesefindings suggest that serum ITIH3 is a candidate biomarker associatedwith gastric cancer progression and tumor microenvironmental alterations,warranting further clinical validation.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5562–5583"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093536","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}

引用次数: 0

Proteomic Insights Reveal TpSH3A with Dual Roles in Cellulases and Oxidative Stress Response in Talaromyces Pinophilus 蛋白质组学研究揭示TpSH3A在Talaromyces Pinophilus纤维素酶和氧化应激反应中具有双重作用

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2026-10-02 Epub Date: 2026-09-02 DOI: 10.1021/acs.jproteome.6c00411

Shivam Aggarwal, Kajal Tyagi, Inderjeet Kaur, Ankit Prakashchandra Jain, Nidhi Adlakha

{"title":"Proteomic Insights Reveal TpSH3A with Dual Roles in Cellulases and Oxidative Stress Response in Talaromyces Pinophilus","authors":"Shivam Aggarwal, Kajal Tyagi, Inderjeet Kaur, Ankit Prakashchandra Jain, Nidhi Adlakha","doi":"10.1021/acs.jproteome.6c00411","DOIUrl":"https://doi.org/10.1021/acs.jproteome.6c00411","url":null,"abstract":"SH3domain-containing proteins mediate protein–proteininteractions,facilitate membrane localization, and regulate intracellular signalingpathways in eukaryotes. Although cellulolytic fungi harbor multipleSH3-containing proteins, their roles in cellulase secretion and stressadaptation have never been studied. This study identified 25 SH3-domain-containingproteins in the model cellulolytic filamentous fungus Talaromyces pinophilus. Transcriptomic analysis furtherrevealed a FUS1p homolog SH3 protein, TpSH3A, which wasuniquely downregulated in the presence of cellulose. Functional characterizationof TpSH3A using knockout and complementation analyses demonstratedthat deletion of Tpsh3a adversely affects fungalgrowth, while concomitantly enhancing the secretion of cellulose-degradingenzymes. Interestingly, the ΔTpsh3a strainexhibited pronounced sensitivity to oxidative and endoplasmic reticulumstress, as evidenced by impaired growth under allyl alcohol and hydrogenperoxide, an attenuated unfolded protein response, and dysregulatedreactive oxygen species homeostasis. Quantitative differential proteomicanalysis showed coordinated downregulation of proteins involved inrespiration, ATP generation, and the unfolded protein response, alongwith upregulation of β-glucosidases, indicating a role in cellularenergy metabolism and secretory output. In concordance, pull-downanalyses suggested that TpSH3A interacts with proteins involved inoxidative phosphorylation, intracellular transport, and membrane organization.These findings highlight TpSH3A as an important factor linking environmentalsensing with enzyme secretion, optimizing T. pinophilus’s capacity for biomass degradation.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":"25 10","pages":"5440–5451"},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093657","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}

引用次数: 0