Journal of proteomics最新文献

{"title":"Expression of concern for 'Evaluation of electron spin resonance for studies of superoxide anion production by human neutrophils interacting with Staphylococcus aureus and Staphylococcus epidermidis', [J. Proteom. (Formerly J. Biochem. Biophys. Meth.) 70(6) (2008) 1059-1065].","authors":"Helen Lundqvist, Staffan Dånmark, Uno Johansson, Håkan Gustafsson, Karin Öllinger","doi":"10.1016/j.jprot.2026.105701","DOIUrl":"10.1016/j.jprot.2026.105701","url":null,"abstract":"","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"331 ","pages":"105701"},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880809","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":"Surface and whole-cell lysate glycomic profiling reveals N-glycosylation features associated with metastatic potential in non-small cell lung cancer.","authors":"Seojeong Lee, Haeun Byeon, Chi Soo Park, Chulmin Moon, Daeun Eom, Siwon Kim, Jihyeon Lee, Yejin Park, Taeyong An, Ha Hyung Kim","doi":"10.1016/j.jprot.2026.105741","DOIUrl":"https://doi.org/10.1016/j.jprot.2026.105741","url":null,"abstract":"<p><p>Cell-surface N-glycans mediate interactions with the tumor microenvironment, whereas whole-cell lysate N-glycans reflect glycoprotein biosynthesis and maturation along the endoplasmic reticulum-Golgi pathway. Although glycomic analyses have revealed cancer-associated N-glycan alterations, the relationship between surface and lysate N-glycomes and metastasis-associated N-glycosylation in non-small cell lung cancer (NSCLC) remains poorly understood. In this study, surface and lysate N-glycomes of the NSCLC cell lines A549 (lower metastatic potential) and H1299 (higher metastatic potential) were profiled using liquid chromatography-electrospray ionization-high-energy collision dissociation tandem mass spectrometry (LC-ESI-HCD-MS/MS), enabling structural characterization with high mass accuracies below 2.0 ppm and relative quantification of individual N-glycans. A total of 59 surface and 54 lysate N-glycans were identified in A549, whereas 70 surface and 71 lysate N-glycans were identified in H1299. Surface N-glycomes were enriched in mature complex-type glycans (55.9% in A549 and 60.0% in H1299), whereas lysates were enriched in high-mannose glycans (49.3% and 40.7%), reflecting distinct stages of glycoprotein maturation. Across surface and lysate N-glycomes, N-acetyllactosamine, a precursor of Lewis x and sialyl Lewis x, was similarly distributed in A549 and H1299; however, H1299 cells displayed consistent enrichment of fucosylation (41.0% in surface and 52.3% in lysate), tri-/tetra-antennary branching (7.3% and 17.8%), Lewis x (4.7% and 4.2%) and sialyl Lewis x (0.1% and 0.1%), representing N-glycosylation features associated with the higher metastatic of H1299 cells. This study provides the first integrated glycomic characterization of metastasis-associated N-glycosylation features across surface and lysate and quantitatively characterizes their association with the metastatic phenotype.</p>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":" ","pages":"105741"},"PeriodicalIF":3.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182503","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":"Ablation of ACSS2 drives alteration to cardiac and hepatic proteomic landscapes in a tissue- and sex-specific manner","authors":"Alexis M. Winters ,&nbsp;Jessica Wohlfahrt ,&nbsp;Tiara Wolf ,&nbsp;Ankita Sarkar ,&nbsp;Suraj J. Patel ,&nbsp;Jennifer Guergues ,&nbsp;Brant R. Burkhardt ,&nbsp;Stanley M. Stevens Jr.","doi":"10.1016/j.jprot.2026.105623","DOIUrl":"10.1016/j.jprot.2026.105623","url":null,"abstract":"<div><div>ACSS2 catalyzes the conversion of acetate into acetyl-CoA, linking nutrient availability to cellular processes such as lipid biosynthesis, energy production, and epigenetic regulation. Although ACSS2 has been studied under metabolically stressful conditions, its basal sex- and tissue-specific functions remain poorly defined. Here, we employed comprehensive proteomic characterization of the impact of global ACSS2 ablation in the liver and heart of adult male and female mice. Over 6000 proteins were identified per tissue, providing deep proteomic coverage. Despite the liver exhibiting greater baseline abundance of ACSS2, the most extensive remodeling occurred in the heart. Both tissues displayed marked sex differences, with males showing greater overall proteomic shifts, and minimal overlap in differentially abundant proteins occurring between males and females. Shared alterations across tissues converged on metabolic and immune regulation, whereas sex-specific changes implicated distinct structural and signaling pathways. Comparatively modest hepatic changes may reflect compensatory processes in the liver, in contrast to the strong inhibitory remodeling observed in the heart. These findings reveal a previously unrecognized degree of tissue- and sex-specificity in regulation by ACSS2, while also highlighting the importance of including female mice in proteomic studies, as male only approaches may overlook key sex-dependent adaptations.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"327 ","pages":"Article 105623"},"PeriodicalIF":2.8,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146154220","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":"Label-free proteomics revealed drought stress tolerance mechanisms in the sugar beet monosomic addition line M14","authors":"Xinyi Guo,&nbsp;Wenjing Qiu,&nbsp;Jiaming Zhu,&nbsp;Yingxiao He,&nbsp;Bing Yu","doi":"10.1016/j.jprot.2026.105608","DOIUrl":"10.1016/j.jprot.2026.105608","url":null,"abstract":"<div><div>Sugar beet M14 line is a diploid cultivated sugar beet (<em>Beta vulgaris</em> L.) that carries a monosomic addition of chromosome 9 from the wild white-flowered beet (<em>B. corolliflora</em> Zoss.), developed through distant hybridization. It exhibits enhanced salt and drought tolerance compared to the diploid cultivated beets. In this study, the M14 line exhibited superior water retention capacity under dehydration conditions compared with five major diploid cultivated varieties grown in northern China. Through integrated analysis of phenotype, photosynthetic parameters, physiological and biochemical indicators, and the expression of key drought-responsive genes, 3 days and 5 days of 20% PEG-6000 treatment were identified as two critical time points for the drought stress response of the M14 line. Through label-free quantitative proteomics, 903 and 526 DAPs were identified at 3 and 5 days, respectively. PPI network analysis further revealed key protein interaction modules in the M14 line under drought stress. Furthermore, qRT-PCR analysis of 12 key DAP-encoding genes revealed that their transcript levels generally corresponded to the protein expression trends. This study helped to produce molecular network maps of drought tolerance in the M14 line, uncovering the mechanisms underlying its drought tolerance.</div></div><div><h3>Significance</h3><div>The drought tolerance of the sugar beet M14 line and ive major diploid sugar beet varieties cultivated in northern China was evaluated, revealing that the M14 line showed the strongest drought resistance. This study uncovered the dynamic regulatory network responsible for drought tolerance in the M14 line at the proteomic level, highlighting the main response pathways and key functional proteins at 3 and 5 days after stress exposure. These results not only deepen our understanding of the molecular mechanisms behind the sugar beet drought tolerance but also identify important candidate proteins and key regulatory modules for molecular breeding drought-tolerant varieties.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"327 ","pages":"Article 105608"},"PeriodicalIF":2.8,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046663","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 amaranth and quinoa seeds reveals species-specific solubility traits of 11S globulins after Osborne and polarity-based extractions","authors":"Esaú Bojórquez-Velázquez ,&nbsp;Abraham M. Vidal-Limón ,&nbsp;Jesús Alejandro Zamora-Briseño ,&nbsp;Miriam L. Llamas-García ,&nbsp;Alberto Barrera-Pacheco ,&nbsp;Eduardo Espitia-Rangel ,&nbsp;Ana P. Barba de la Rosa","doi":"10.1016/j.jprot.2026.105621","DOIUrl":"10.1016/j.jprot.2026.105621","url":null,"abstract":"<div><div>Amaranth and quinoa are nutritious grains rich in essential amino acids, vitamins, and phytochemicals. The use of these emergent functional foods is still limited and their proteins are poorly characterized. Here, we compared amaranth and quinoa seeds by profiling their proteins using Osborne and polarity-based extraction methods and evaluating their relative protein content. The Osborne fractions and the two fractions generated by the polarity-based method (hydrophilic and hydrophobic) were quantified and analyzed by 1D-SDS-PAGE in the absence and presence of a reducing agent, as well as by diagonal electrophoresis. In addition, hydrophilic and hydrophobic proteins were analyzed by 2-DE, and the representative spots for each species were identified by LC-MS/MS. Both methods yield similar total protein amounts. The electrophoretic profiles showed differentiated patterns between the two seeds. All the extracts reflect the formation of high-molecular-mass aggregates because of interchain disulfide bonds. Intrachain disulfide bonds were also detected in 2S albumins. A differential behavior in the solubility of 11S globulins was observed across both species, and molecular modelling and molecular dynamics simulations were performed to explain this phenomenon. This study provides valuable insights into the structural differences between amaranth and quinoa proteins, which could help inform decisions about potential food applications.</div></div><div><h3>Significance</h3><div>This work addresses two main topics: the implementation of alternative methods for characterizing plant proteins and the detailed comparison of the protein profiles of amaranth and quinoa seeds using different electrophoretic approaches. The polarity-based method we propose represents an alternative to reduce sample handling and the number of extracts required for proteome characterization without sacrificing the protein yield. This study generated relevant information on the storage proteins of the two seeds analyzed, primarily 2S albumins, prolamins, and 11S globulins, to inform decision-making on their application in food technology.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"327 ","pages":"Article 105621"},"PeriodicalIF":2.8,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137156","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":"Proteomics-driven innovations in plant-based foods: Current advances, emerging technologies, and future perspectives","authors":"Fatma Boukid","doi":"10.1016/j.jprot.2026.105624","DOIUrl":"10.1016/j.jprot.2026.105624","url":null,"abstract":"<div><div>Despite rapid market growth, plant-based foods such as meat analogs, plant-based milk, yogurt alternatives, and fermented products still fall short of matching the sensory, structural, and nutritional qualities of animal-based counterparts, primarily due to simple ingredient substitution that fails to reproduce the molecular structure, interactions, and functional properties required for optimal texture, flavor, and nutritional performance. Proteomics, using advanced mass spectrometry (MS) and label-free quantification methods, provides an approach to analyze plant protein composition, structure, interactions, and modifications, enabling targeted functional improvements. This review describes how proteomic workflows inform formulation across three areas. First, protein compositional and structural characterization employs techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) and differential scanning calorimetry (DSC) coupled with MS to map protein composition and structural behavior, supporting decisions on protein sources, fractionation, and purification. Second, indirect proteomic methods coupled with other non-proteomic complementary tools are used to determine structure–function relationships induced by processing to examine processing-induced crosslinking, enzymatic modifications, and lipid–protein interactions that influence texture. Third, targeted MS methods, including selected reaction monitoring (SRM) and parallel reaction monitoring (PRM), are applied to profile off-flavor compounds and identify protein modification sites relevant to sensory and nutritional properties. By integrating proteomic data with processing strategies, this review outlines how proteomics can be used to examine key functional attributes related to texture, flavor, and nutritional quality in plant-based foods.</div></div><div><h3>Significance</h3><div>This review highlights the pivotal role of proteomics in advancing next-generation plant-based foods. Proteomic analysis enables an in-depth understanding of plant protein structure, composition, interactions, and bioactivity, providing critical insights for the development of functionally enhanced and consumer-acceptable alternatives. By integrating proteomics with AI, machine learning, multi-omics approaches, and cutting-edge analytical tools such as spatial proteomics and mass spectrometry imaging, the review demonstrates how protein functionality, flavor, texture, nutrition, and allergenicity can be optimized. Furthermore, it emphasizes the potential of proteomics to accelerate innovation in personalized nutrition, support sustainable and circular food systems, improve food safety, and reduce waste by valorizing plant-based by-products. This work serves as a roadmap for researchers and industry stakeholders seeking to leverage proteomics to design novel, high-quality, and sustainable plant-based protein products.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"327 ","pages":"Article 105624"},"PeriodicalIF":2.8,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146154196","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":"Barley protein: From agricultural staple to sustainable protein solution","authors":"Fatma Boukid","doi":"10.1016/j.jprot.2026.105603","DOIUrl":"10.1016/j.jprot.2026.105603","url":null,"abstract":"<div><div>Barley protein is a multifunctional, sustainable plant-based ingredient with potential in food, nutraceutical, and industrial applications. This review synthesizes current knowledge on barley protein, emphasizing how proteomics and processing methods influence its composition, digestibility, and functional properties. Proteomic analyses reveal the distribution of major protein fractions, albumins, globulins, hordeins, and glutelins and their bioactive peptides, which exhibit antioxidant, antihypertensive, antidiabetic, and appetite-regulating activities. Protein concentrates and isolates offer improved digestibility and functional quality, though lysine remains limiting. Advanced techniques, including enzymatic hydrolysis, ultrasound-assisted extraction, and post-processing modifications, are evaluated for their impact on protein structure and functionality. Barley protein's potential applications in novel foods, micro- and nano-encapsulation, and targeted bioactive delivery are highlighted. By integrating proteomics insights with nutritional and technological perspectives, this work underscores the role of barley proteins in sustainable food systems.</div></div><div><h3>Significance</h3><div>This review synthesizes current knowledge on barley protein composition, emphasizing insights gained from proteomic analyses. By characterizing protein fractions, bioactive peptides, and allergenic determinants, proteomics enables a deeper understanding of barley's functional, nutritional, and health-related properties. The work highlights how extraction and processing influence protein quality and bioactivity, informing strategies for the development of novel plant-based foods. These insights provide a foundation for future research and industrial applications, advancing barley as a sustainable and functional protein source in human nutrition.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"326 ","pages":"Article 105603"},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003744","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":"Sputum proteomics and phosphoproteomics for improving chronic obstructive pulmonary disease knowledge","authors":"Fei Long ,&nbsp;Xiaoyin Zeng ,&nbsp;Fengyan Wang ,&nbsp;Xufei Wang ,&nbsp;Weijuan Shi ,&nbsp;Yanting Lan ,&nbsp;Jiahao Cheng ,&nbsp;Chen Zhu ,&nbsp;Yiqi Yang ,&nbsp;Jing Xiao ,&nbsp;Longbo Hu ,&nbsp;Long Tan ,&nbsp;Yuqiong Yang ,&nbsp;Rongchang Chen ,&nbsp;Zhenyu Liang ,&nbsp;Tao Peng ,&nbsp;Shaohua Lu","doi":"10.1016/j.jprot.2026.105605","DOIUrl":"10.1016/j.jprot.2026.105605","url":null,"abstract":"<div><div>Analysis of proteins and other molecular components in induced sputum provides critical insights for the diagnosis, pathological assessment, and therapeutic monitoring of respiratory diseases. In this study, we collected three distinct types of induced sputum samples from patients with chronic obstructive pulmonary disease (COPD) and subjected them to proteomic and phosphoproteomic analysis using three different enzymatic digestion methods. We found that raw sputum samples yielded a higher number of uniquely identified proteins and phosphoproteins (1313 proteins and 1603 phosphorylation sites, corresponding to 782 phosphoproteins) and provided a more comprehensive characterization of COPD pathology. Furthermore, compared to in-gel digestion and in-solution digestion, the filter-aided sample preparation method increased protein identification by approximately 30% and yielded the highest number of unique protein identifications. Our study is the first to demonstrate that raw induced sputum can serve as a viable alternative source for liquid biopsy in respiratory diseases. We have also established the first methodological framework and dataset for proteomic and phosphoproteomic analysis of raw induced sputum, generating a preliminary map of the COPD sputum proteome and phosphoproteome. This novel proteomic and phosphoproteomic approach has untangled biologically relevant pathways in respiratory physiology, highlighting potential avenues for future research.</div></div><div><h3>Significance</h3><div>In this study, we aimed to investigate the feasibility of establishing and evaluating proteomic research methods using sputum samples from patients with chronic obstructive pulmonary disease (COPD). The ultimate goal was to develop analytical approaches suitable for sputum proteomics and phosphoproteomics and to preliminarily map the sputum proteome and phosphoproteome in COPD. It was found that raw sputum samples more comprehensively reflect the disease characteristics of COPD and are therefore more suitable for proteomic and phosphoproteomic studies of COPD. Among three mainstream enzymatic digestion methods, the Filter-Aided Sample Preparation (FASP) method demonstrated superior identification rates and was deemed most suitable for processing raw sputum samples. Furthermore, this study reports for the first time a draft map of the proteome and phosphoproteome of COPD sputum. This research provides valuable insights into sputum proteomic analysis and offers a useful resource for the study of respiratory diseases.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"326 ","pages":"Article 105605"},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018988","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":"Rapid high-throughput antibody analysis using microwave-assisted digestion","authors":"Thais Mingatos de Toledo ,&nbsp;Hellen Paula Valerio ,&nbsp;Antônio Moreira Marques Neto ,&nbsp;Simon Ngao Mule ,&nbsp;Priscila Robertina dos Santos Donado ,&nbsp;Claudia Blanes Angeli Pascale ,&nbsp;Giuseppe Palmisano","doi":"10.1016/j.jprot.2026.105601","DOIUrl":"10.1016/j.jprot.2026.105601","url":null,"abstract":"<div><div>Monoclonal antibodies are a class of biotherapeutic proteins that have been developed over the past decade, leading to improved standards of care for the treatment of multiple diseases. Multi-attribute methods have emerged as powerful tools for critical quality attributes (CQAs). They leverage high-resolution accurate mass spectrometry and automated computational pipelines to identify pre-established modifications using DDA. In this study, we describe the development of a mass spectrometry–based workflow capable of processing up to 96 samples simultaneously while monitoring a broad panel of PTMs. We evaluated microwave-assisted digestion under different buffers and pHs, assessing sequence coverage, missed cleavages, and the occurrence of chemical artifacts. Analyses were performed using both DDA and DIA. Raw data were processed in dependent-peptide search(DDA) and PTM-probing search(DIA), enabling PTM discovery without prior knowledge. Our results demonstrate that microwave-assisted digestion, combined with control of temperature and pH, provides a fast and reliable alternative for efficiently digesting biotherapeutic proteins. It achieves high sequence coverage while minimizing artificial PTM formation. We also show that DIA combined with MW digestion improved peptide identification, highlighting its potential for comprehensive characterization of antibodies. Among the tested buffers, sodium acetate under MW conditions was the most effective in reducing deamidation and oxidation levels.</div></div><div><h3>Significance</h3><div>This study presents a detailed and optimized protocol for microwave-assisted (MW) protein digestion, enabling simultaneous reduction and alkylation for antibody samples. The method is rapid and minimizes chemical artifacts typically introduced during sample preparation. By combining MW-assisted digestion with both data-dependent (DDA) and data-independent acquisition (DIA), we performed a comprehensive and unbiased multi-attribute analysis (MAM). Notably, the use of DIA alongside MW digestion allowed for higher reproducibility and more complete peptide and post-translational modification (PTM) detection compared to DDA alone. Compared to conventional overnight digestion, MW-assisted digestion significantly reduced deamidation levels, with evident influences of buffer composition and pH on PTM identification. Although the levels of protein oxidation persisted, indicating that further optimization is necessary, this approach substantially decreased other artifacts, particularly deamidation, highlighting its potential as a fast, reliable, and highly informative strategy for antibody characterization.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"326 ","pages":"Article 105601"},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030053","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":"Prospective serial proteomic analysis uncovers mechanistic pathways of chemotherapy resistance in advanced non-small cell lung cancer","authors":"Wei-Ke Kuo ,&nbsp;Hsin-Yu Chu ,&nbsp;Yen-Kun Ko ,&nbsp;Pang-Hung Hsu","doi":"10.1016/j.jprot.2026.105620","DOIUrl":"10.1016/j.jprot.2026.105620","url":null,"abstract":"<div><div>Predicting chemotherapy response in advanced non-small cell lung cancer (NSCLC) remains a clinical challenge, as baseline profiles often fail to capture dynamic molecular adaptations under treatment. This prospective study employed serial plasma proteomics to identify mechanistic pathways associated with chemotherapy resistance in 44 patients with stage IV NSCLC receiving platinum-based doublet chemotherapy. By analyzing blood samples collected immediately before the first and second cycles using liquid chromatography-tandem mass spectrometry, we demonstrated that a ratio-based proteomic model (early-treatment/pre-treatment) yielded superior separation between controlled and uncontrolled disease (UCD) compared to baseline-only assessment. Among 159 quantified proteins, 13 showed significant differential abundance, with UCD patients exhibiting marked upregulation of tetranectin, coagulation factor XIII A chain, and complement factor H-related protein 2. Ingenuity Pathway Analysis revealed that therapeutic resistance was characterized by three dominant axes: the activation of complement-coagulation-acute-phase signaling, the induction of lipid-nuclear receptor activity (LXR/RXR and DHCR24 signaling), and the relative attenuation of immune-regulatory pathways such as IL-12 signaling. These findings highlight the potential of serial proteomic profiling to uncover treatment-induced molecular adaptations, providing insights for therapeutic monitoring and hypothesis generation in precision oncology.</div></div><div><h3>Significance</h3><div>This study demonstrates the added value of prospective serial plasma proteomic profiling, compared with baseline-only approaches, for capturing early treatment-associated molecular adaptations in advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. By quantifying proteomic changes between pre-treatment and early-treatment time points, we identified coordinated alterations involving the complement–coagulation–acute-phase axis and lipid–nuclear receptor signaling programs, including LXR/RXR and DHCR24, alongside relative attenuation of immune-regulatory pathways.</div><div>Rather than reflecting isolated protein effects, these findings highlight interconnected host–tumor response programs that emerge under therapeutic pressure and may contribute to early adaptive resistance. Importantly, this work moves beyond static baseline markers by emphasizing dynamic, pathway-level changes and provides a hypothesis-generating framework for longitudinal therapeutic monitoring. Candidate proteins such as tetranectin and coagulation factor XIII A chain are proposed as molecular features associated with treatment response, warranting further validation in larger, prospective cohorts before translational application.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"326 ","pages":"Article 105620"},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137258","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}