PROTEOMICS – Clinical Applications最新文献

{"title":"Identification of novel biomarkers for frailty diagnosis via serum amino acids metabolomic analysis using UPLC-MS/MS.","authors":"Mengyuan Zhou, Wenjing Sun, Jiaojiao Chu, Yingping Liao, Pengfei Xu, Xujiao Chen, Meng Li","doi":"10.1002/prca.202300035","DOIUrl":"10.1002/prca.202300035","url":null,"abstract":"<p><strong>Purpose: </strong>This study was aimed to analyze serum amino acid metabolite profiles in frailty patients, gain a better understanding of the metabolic mechanisms in frailty, and assess the diagnostic value of metabolomics-based biomarkers of frailty.</p><p><strong>Experimental design: </strong>This study utilized the ultra-performance liquid chromatography tandem mass spectrometry to examine amino acids associated with frailty. Additionally, we employed multivariate statistical methods, metabolomic data analysis, receiver operating characteristic (ROC) curve analysis, and pathway enrichment analysis.</p><p><strong>Results: </strong>Among the assayed amino acid metabolites, we identified biomarkers for frailty. ROC curve analysis for frailty diagnosis based on the modified Fried's frailty index showed that the areas under ROC curve of tryptophan, phenylalanine, aspartic acid, and combination were 0.775, 0.679, 0.667, and 0.807, respectively. ROC curve analysis for frailty diagnosis based on Frail Scale showed that the areas under ROC curve of cystine, phenylalanine, and combination of amino acids (cystine, L-Glutamine, citrulline, tyrosine, kynurenine, phenylalanine, glutamin acid) were 0.834, 0.708, and 0.854 respectively.</p><p><strong>Conclusion and clinical relevance: </strong>In this study, we explored the serum amino acid metabolite profiles in frailty patients. These present metabolic analyses may provide valuable information on the potential biomarkers and the possible pathogenic mechanisms of frailty.</p><p><strong>Clinical significance: </strong>Frailty is a clinical syndrome, as a consequence it is challenging to identify at early course of the disease, even based on the existing frailty scales. Early diagnosis and appropriate patient management are the key to improve the survival and limit disabilities in frailty patients. Proven by the extensive laboratory and clinical studies on frailty, comprehensive analysis of metabolic levels in frail patients, identification of biomarkers and study of pathogenic pathways of metabolites contribute to the prediction and early diagnosis of frailty. In this study, we explored the serum amino acid metabolite profiles in frailty patients. These present metabolic analyses may provide valuable information on the potential biomarkers and the possible pathogenic mechanisms of frailty.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404069","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}

{"title":"Screening of novel biomarkers for acute kidney transplant rejection using DIA-MS based proteomics.","authors":"Ce Wang, Gang Feng, Jie Zhao, Yang Xu, Yang Li, Lin Wang, Meng Wang, Miao Liu, Yilin Wang, Hong Mu, Chunlei Zhou","doi":"10.1002/prca.202300047","DOIUrl":"10.1002/prca.202300047","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation is the preferred treatment for patients with end-stage renal disease. However, acute rejection poses a threat to the graft long-term survival. The aim of this study was to identify novel biomarkers to detect acute kidney transplant rejection.</p><p><strong>Methods: </strong>The serum proteomic profiling of kidney transplant patients with T cell-mediated acute rejection (TCMR) and stable allograft function (STA) was analyzed using data-independent acquisition mass spectrometry (DIA-MS). The differentially expressed proteins (DEPs) of interest were further verified by enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>A total of 131 DEPs were identified between STA and TCMR patients, 114 DEPs were identified between mild and severe TCMR patients. The verification results showed that remarkable higher concentrations of serum amyloid A protein 1 (SAA1) and insulin like growth factor binding protein 2 (IGFBP2), and lower fetuin-A (AHSG) concentration were found in TCMR patients when compared with STA patients. We also found higher SAA1 concentration in severe TCMR group when compared with mild TCMR group. The receiver operating characteristics (ROC) analysis further confirmed that combination of SAA1, AHSG, and IGFBP2 had excellent performance in the acute rejection diagnosis.</p><p><strong>Conclusions: </strong>Our data demonstrated that serum SAA1, AHSG, and IGFBP2 could be effective biomarkers for diagnosing acute rejection after kidney transplantation. DIA-MS has great potential in biomarker screening of kidney transplantation.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432881","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}

{"title":"Comprehensive characterization of protein modifications using mass spectrometry and dry blood spots.","authors":"Sofia Guedes, Luís Perpétuo, Jacinta Veloso, Tânia Lima, Ana F Ferreira, Inês Pires, Francisca Savaiva, André Lourenço, Liliana Moreira-Costa, Adelino Leite-Moreira, Antonio Barros, Fábio Trindade, Rui Vitorino","doi":"10.1002/prca.202300102","DOIUrl":"10.1002/prca.202300102","url":null,"abstract":"<p><strong>Purpose: </strong>The main objective of this study is to characterize and analyze modified peptides in DBS samples. This includes deciphering their specific PTMs and understanding their potential impact on the population or disease cohort under study.</p><p><strong>Experimental design: </strong>Using mass spectrometry-based proteomic approaches, we performed a comprehensive analysis of DBS samples. Our focus was on the identification and quantification of modified peptides. We also took advantage of recent advances in DBS mass spectrometry to ensure accurate detection and quantification.</p><p><strong>Results: </strong>A comprehensive analysis identified 972 modified peptides in DBS samples. Of these, a subset of 211 peptides was consistently present in all samples, highlighting their potential biological importance and relevance. This indicates a diverse spectrum of PTMs in the proteome of DBS samples.</p><p><strong>Conclusions and clinical relevance: </strong>Integration of mass spectrometry and proteomics has revealed a broad spectrum of modified peptides in DBS samples and highlighted their importance in biological processes and disease progression. Accurate detection of these PTMs may be critical for risk stratification and disease management. This study improves the understanding of molecular mechanisms underlying biological processes and disease development, providing important insights for clinical applications.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088133","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}

{"title":"Potential functionality of Cutibacterium acnes extracellular vesicles in atopic dermatitis and acne vulgaris: A comparative proteomic analysis","authors":"Tianze Yu, Jin Chen, Shi Wu, Min Jiang, Ling Han, Ying Ma","doi":"10.1002/prca.202300106","DOIUrl":"https://doi.org/10.1002/prca.202300106","url":null,"abstract":"Background<jats:italic>Cutibacterium acnes</jats:italic> is a commensal bacterium residing in healthy skin and plays a critical role in maintaining skin homeostasis. <jats:italic>C. acnes</jats:italic> has been considered closely related to acne vulgaris, while recent studies suggest that <jats:italic>C. acnes</jats:italic> and its metabolites may have a protective role in atopic dermatitis (AD) by modulating the immune system and maintaining skin homeostasis. Extracellular vesicles (EVs) are small membranous vesicles secreted by bacteria that participate in bacteria‐host interactions.MethodsThis study first compared <jats:italic>C. acnes</jats:italic> EVs from AD lesions (AD‐EVs), acne lesions (Acne‐EVs), and healthy skin (NC‐EVs), using Label‐free quantitative LC‐MS/MS and validated differently expressed proteins by parallel reaction monitoring (PRM). Then Normal Human Epidermal Keratinocytes (NHEK) and human primary keratinocytes (KC) were treated with <jats:italic>C. acnes</jats:italic> EVs isolated from different groups, and the expressions of inflammatory factors were measured by quantitative real‐time PCR and Western blotting.ResultsCompared with the acne group, the AD group showed greater downregulation of proteins related to energy metabolism and carbon source utilization pathway. Differences in protein profile in AD and acne lesion‐separated <jats:italic>C. acnes</jats:italic> EVs correspond to the abnormal sebum secretion pattern in both diseases. <jats:italic>C. acnes</jats:italic> EVs from different groups affected different expressions of Th1 and Th2 inflammatory factors and epidermal barrier markers in NHEK and KC, indicating different immunomodulatory potentials.ConclusionsThis study observed distinct proteomic differences between AD‐EVs and Acne‐EVs, and provided insights into the functional differences of <jats:italic>C. acnes</jats:italic> EVs in AD and acne.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627933","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}

{"title":"Proteomic and metabolomic characterization of bone, liver, and lung metastases in plasma of breast cancer patients","authors":"Hui Ye, Xiabo Shen, Yaohan Li, Weibin Zou, Syed Shams ul Hassan, Yue Feng, Xiaojia Wang, Jingkui Tian, Xiying Shao, Yi Tao, Wei Zhu","doi":"10.1002/prca.202300136","DOIUrl":"https://doi.org/10.1002/prca.202300136","url":null,"abstract":"BackgroundBreast cancer (BC) is the second leading cause of cancer‐related deaths among women, primarily due to metastases to other organs rather than the primary tumor.MethodsIn this study, a comprehensive analysis of plasma proteomics and metabolomics was conducted on a cohort of 51 BC patients. Potential biomarkers were screened by the Least Absolute Shrinkage and Selection Operator (LASSO) regression and Random Forest algorithm. Additionally, enzyme‐linked immunosorbent assay (ELISA) kits and untargeted metabolomics were utilized to validate the prognostic biomarkers in an independent cohort.ResultsIn the study, extracellular matrix (ECM)‐related functional enrichments were observed to be enriched in BC cases with bone metastases. Proteins dysregulated in retinol metabolism in liver metastases and leukocyte transendothelial migration in lung metastases were also identified. Machine learning models identified specific biomarker panels for each metastasis type, achieving high diagnostic accuracy with area under the curve (AUC) of 0.955 for bone, 0.941 for liver, and 0.989 for lung metastases.ConclusionsFor bone metastasis, biomarkers such as leucyl‐tryptophan, LysoPC(P‐16:0/0:0), FN1, and HSPG2 have been validated. dUDP, LPE(18:1/0:0), and aspartylphenylalanine have been confirmed for liver metastasis. For lung metastasis, dUDP, testosterone sulfate, and PE(14:0/20:5) have been established.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603350","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}

{"title":"Comprehensive profiling of the human fecal proteome from IBD patients with DIA-MS enables evaluation of disease-relevant proteins.","authors":"Brandon J Harder, Annemarie N Lekkerkerker, Ellen P Casavant, Jason A Hackney, Allen Nguyen, Jacqueline M McBride, William Rodney Mathews, Veronica G Anania","doi":"10.1002/prca.202300075","DOIUrl":"https://doi.org/10.1002/prca.202300075","url":null,"abstract":"<p><strong>Purpose: </strong>Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by chronic gastrointestinal inflammation. A high unmet need exists for noninvasive biomarkers in IBD to monitor changes in disease activity and guide treatment decisions. Stool is an easily accessed, disease proximal matrix in IBD, however the composition of the IBD fecal proteome remains poorly characterized.</p><p><strong>Experimental design: </strong>A data-independent acquisition LC-MS/MS approach was used to profile the human fecal proteome in two independent cohorts (Cohort 1: healthy n = 5, UC n = 5, CD n = 5, Cohort 2: healthy n = 20, UC n = 10, and CD n = 10) to identify noninvasive biomarkers reflective of disease activity.</p><p><strong>Results: </strong>688 human proteins were quantified, with 523 measured in both cohorts. In UC stool 96 proteins were differentially abundant and in CD stool 126 proteins were differentially abundant compared to healthy stool (absolute log2 fold change > 1, p-value < 0.05). Many of these fecal proteins are associated with infiltrating immune cells and ulceration/rectal bleeding, which are hallmarks of IBD pathobiology. Mapping the identified fecal proteins to a whole blood single-cell RNA sequencing data set revealed the involvement of various immune cell subsets to the IBD fecal proteome.</p><p><strong>Conclusions and clinical relevance: </strong>Findings from this study not only confirmed the presence of established fecal biomarkers for IBD, such as calprotectin and lactoferrin, but also revealed new fecal proteins from multiple pathways known to be dysregulated in IBD. These novel proteins could serve as potential noninvasive biomarkers to monitor specific aspects of IBD disease activity which could expedite clinical development of novel therapeutic targets.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327067","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}

{"title":"Masthead: Proteomics 2'24","authors":"","doi":"10.1002/prca.202470023","DOIUrl":"https://doi.org/10.1002/prca.202470023","url":null,"abstract":"","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140106254","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}

{"title":"Editorial Board: Proteomics 2'24","authors":"","doi":"10.1002/prca.202470022","DOIUrl":"https://doi.org/10.1002/prca.202470022","url":null,"abstract":"","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140106334","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}

{"title":"N-glycosylation of disease-specific haptoglobin for the early screening of diabetic retinopathy.","authors":"Zhonghao Yuan, Zhizhen Lai, Yixin Zhang, Jiyun Zhang, Jinyu Zhou, Dan Li, Weihong Yu, Jiang Zhou, Zhili Li","doi":"10.1002/prca.202300032","DOIUrl":"https://doi.org/10.1002/prca.202300032","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic retinopathy (DR), as one of the microvascular complications of diabetes, is a leading cause of acquired vision loss. Most DR cases are detected in the advanced stage through fundoscopy, making molecular biomarkers urgently needed for early diagnosis of DR.</p><p><strong>Experimental design: </strong>Serum disease-specific haptoglobin-β (Hp-β) chains of 100 patients with type 2 diabetes mellitus (T2DM) and 156 T2DM patients with non-proliferative diabetic retinopathy (NPDR) were separated using polyacrylamide gel electrophoresis. After in-gel digestion and enrichment, the intact N-glycopeptides were detected by mass spectrometry.</p><p><strong>Results: </strong>Fucosylation of Hp-β was significantly increased and sialylation of Hp-β was significantly decreased in background DR (BDR, an early-stage DR) patients compared with non-diabetic retinopathy patients (p < 0.05) and yielded area under curves (AUCs) of 0.801 and 0.829 in training and validation groups, respectively, which had an advantage over glycated hemoglobin A1c (AUC ≤ 0.691). Moreover, a significant increase in sialylated Hp-β was found in severe NPDR patients compared with BDR patients and yielded an AUC of 0.828 to distinguish severe NPDR from BDR.</p><p><strong>Conclusion: </strong>Changes in Hp-β glycosylation are closely related to DR, and may be used for early diagnosis and screening of DR.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060362","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}

{"title":"Proteomic changes of botulinum neurotoxin injection on muscle growth in children with spastic cerebral palsy.","authors":"Xubo Yang, Hongmei Tang, Lu He, Tingting Peng, Jinling Li, Jingbo Zhang, Liru Liu, Hongyu Zhou, Zhaofang Chen, Jingyi Zhao, Yage Zhang, Mengru Zhong, Mingshan Han, Mengqing Zhang, Huiran Niu, Kaishou Xu","doi":"10.1002/prca.202300070","DOIUrl":"https://doi.org/10.1002/prca.202300070","url":null,"abstract":"<p><strong>Purpose: </strong>The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP).</p><p><strong>Experimental design: </strong>A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting.</p><p><strong>Results: </strong>Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways.</p><p><strong>Conclusion and clinical relevance: </strong>BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060363","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}