Clinical proteomics最新文献

{"title":"ESF1 and MIPEP proteins promote estrogen receptor-positive breast cancer proliferation and are associated with patient prognosis.","authors":"Qing Yu, Chunhua Qu, Jinliang Liang, Peiqi Chen, Kaiying Zhang, Yanji Zhang, Yuening Zhang, Zherui Li, Shaojun Liu, Zhaoshou Yang, Hongyan Sun, Anli Yang","doi":"10.1186/s12014-024-09502-8","DOIUrl":"10.1186/s12014-024-09502-8","url":null,"abstract":"<p><strong>Background: </strong>Estrogen receptor-positive (ER+) breast cancer accounts for two-thirds of all breast cancers, and its early and late recurrences still threaten patients' long-term survival and quality of life. Finding candidate tumor antigens and potential therapeutic targets is critical to addressing these unmet needs.</p><p><strong>Method: </strong>The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to identify the differentially expressed proteins (DEPs) between ER + breast cancer and corresponding adjacent normal tissue. Candidate DEPs were screened by bioinformatic analyses, and their expression was confirmed by immunohistochemical (IHC) staining and western blot. A series of in vitro experiments, including wound healing assay, colony formation, and cell cycle assay, were performed to reveal the functions of selected DEPs. Additionally, their clinical significances were further analyzed.</p><p><strong>Result: </strong>A total of 369 DEPs (fold change ≥ 2.0 or ≤ 0.66, P < 0.05) were discovered. Compared with normal tissue, 358 proteins were up-regulated and 11 proteins were down-regulated in ER + breast cancer. GO and KEGG enrichment analysis showed that DEPs were closely associated with RNA regulation and metabolic pathways. STRING analysis found ESF1 and MIPEP were the hub genes in breast cancer, whose increased expressions were verified by the IHC staining and western blot. Knocking down ESF1 and MIPEP inhibited colony formation and increased cell apoptosis. Besides, knocking down ESF1 inhibited wound healing but not MIPEP. In addition, ESF1 and MIPEP expression were negatively associated with patient prognosis.</p><p><strong>Conclusion: </strong>The upregulation of ESF1 and MIPEP promoted ER + breast cancer proliferation, which might provide novel targets for the development of new therapies.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"50"},"PeriodicalIF":2.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome profiling of cutaneous leishmaniasis lesions due to dermotropic Leishmania donovani in Sri Lanka.","authors":"Nuwani H Manamperi, Nimesha Madhushani Edirisinghe, Harshima Wijesinghe, Lakmali Pathiraja, Nishantha Pathirana, Vishmi Samudika Wanasinghe, Chamalka Gimhani De Silva, W Abeyewickreme, Nadira D Karunaweera","doi":"10.1186/s12014-024-09499-0","DOIUrl":"10.1186/s12014-024-09499-0","url":null,"abstract":"<p><strong>Background: </strong>Characterization of the host response in cutaneous leishmaniasis (CL) through proteome profiling has gained limited insights into leishmaniasis research compared to that of the parasite. The primary objective of this study was to comprehensively analyze the proteomic profile of the skin lesions tissues in patients with CL, by mass spectrometry, and subsequent validation of these findings through immunohistochemical methods.</p><p><strong>Methods: </strong>Eight lesion specimens from leishmaniasis-confirmed patients and eight control skin biopsies were processed for proteomic profiling by mass spectrometry. Formalin-fixed paraffin-embedded lesion specimens from thirty patients and six control skin specimens were used for Immunohistochemistry (IHC) staining. Statistical analyses were carried out using SPSS software. The chi-square test was used to assess the association between the degree of staining for each marker and the clinical and pathological features.</p><p><strong>Results: </strong>Sixty-seven proteins exhibited significant differential expression between tissues of CL lesions and healthy controls (p < 0.01), representing numerous enriched biological processes within the lesion tissue, as evident by both the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Among these, the integrated endoplasmic reticulum stress response (IERSR) emerges as a pathway characterized by the up-regulated proteins in CL tissues compared to healthy skin. Expression of endoplasmic reticulum (ER) stress sensors, inositol-requiring enzyme-1 (IRE1), protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6 (ATF6) in lesion tissue was validated by immunohistochemistry.</p><p><strong>Conclusions: </strong>In conclusion, proteomic profiling of skin lesions carried out as a discovery phase study revealed a multitude of probable immunological and pathological mechanisms operating in patients with CL in Sri Lanka, which needs to be further elaborated using more in-depth and targeted investigations. Further research exploring the intricate interplay between ER stress and CL pathophysiology may offer promising avenues for the development of novel diagnostic tools and therapeutic strategies in combating this disease.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"48"},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single-sample workflow for joint metabolomic and proteomic analysis of clinical specimens.","authors":"Hagen M Gegner, Thomas Naake, Karim Aljakouch, Aurelien Dugourd, Georg Kliewer, Torsten Müller, Dustin Schilling, Marc A Schneider, Nina Kunze-Rohrbach, Thomas G P Grünewald, Rüdiger Hell, Julio Saez-Rodriguez, Wolfgang Huber, Gernot Poschet, Jeroen Krijgsveld","doi":"10.1186/s12014-024-09501-9","DOIUrl":"10.1186/s12014-024-09501-9","url":null,"abstract":"<p><p>Understanding the interplay of the proteome and the metabolome helps to understand cellular regulation and response. To enable robust inferences from such multi-omics analyses, we introduced and evaluated a workflow for combined proteome and metabolome analysis starting from a single sample. Specifically, we integrated established and individually optimized protocols for metabolomic and proteomic profiling (EtOH/MTBE and autoSP3, respectively) into a unified workflow (termed MTBE-SP3), and took advantage of the fact that the protein residue of the metabolomic sample can be used as a direct input for proteome analysis. We particularly evaluated the performance of proteome analysis in MTBE-SP3, and demonstrated equivalence of proteome profiles irrespective of prior metabolite extraction. In addition, MTBE-SP3 combines the advantages of EtOH/MTBE and autoSP3 for semi-automated metabolite extraction and fully automated proteome sample preparation, respectively, thus advancing standardization and scalability for large-scale studies. We showed that MTBE-SP3 can be applied to various biological matrices (FFPE tissue, fresh-frozen tissue, plasma, serum and cells) to enable implementation in a variety of clinical settings. To demonstrate applicability, we applied MTBE-SP3 and autoSP3 to a lung adenocarcinoma cohort showing consistent proteomic alterations between tumour and non-tumour adjacent tissue independent of the method used. Integration with metabolomic data obtained from the same samples revealed mitochondrial dysfunction in tumour tissue through deregulation of OGDH, SDH family enzymes and PKM. In summary, MTBE-SP3 enables the facile and reliable parallel measurement of proteins and metabolites obtained from the same sample, benefiting from reduced sample variation and input amount. This workflow is particularly applicable for studies with limited sample availability and offers the potential to enhance the integration of metabolomic and proteomic datasets.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"49"},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of dynamic exclusion and the use of FAIMS, DIA and MALDI-mass spectrometry imaging with ion mobility on amyloid protein identification.","authors":"Jennifer T Aguilan, Jihyeon Lim, Sabrina Racine-Brzostek, Joshua Fischer, Cristina Silvescu, Shannon Cornett, Edward Nieves, Damodara Rao Mendu, Carlos-Madrid Aliste, Stacia Semple, Ruth Angeletti, Louis M Weiss, Adam Cole, Michael Prystowsky, James Pullman, Simone Sidoli","doi":"10.1186/s12014-024-09500-w","DOIUrl":"10.1186/s12014-024-09500-w","url":null,"abstract":"<p><p>Amyloidosis is a disease characterized by local and systemic extracellular deposition of amyloid protein fibrils where its excessive accumulation in tissues and resistance to degradation can lead to organ failure. Diagnosis is challenging because of approximately 36 different amyloid protein subtypes. Imaging methods like immunohistochemistry and the use of Congo red staining of amyloid proteins for laser capture microdissection combined with liquid chromatography tandem mass spectrometry (LMD/LC-MS/MS) are two diagnostic methods currently used depending on the expertise of the pathology laboratory. Here, we demonstrate a streamlined in situ amyloid peptide spatial mapping by Matrix Assisted Laser Desorption Ionization-Mass Spectrometry Imaging (MALDI-MSI) combined with Trapped Ion Mobility Spectrometry for potential transthyretin (ATTR) amyloidosis subtyping. While we utilized the standard LMD/LC-MS/MS workflow for amyloid subtyping of 31 specimens from different organs, we also evaluated the potential introduction in the MS workflow variations in data acquisition parameters like dynamic exclusion, or testing Data Dependent Acquisition combined with High-Field Asymmetric Waveform Ion Mobility Spectrometry (DDA FAIMS) versus Data Independent Acquisition (DIA) for enhanced amyloid protein identification at shorter acquisition times. We also demonstrate the use of Mascot's Error Tolerant Search and PEAKS de novo sequencing for the sequence variant analysis of amyloidosis specimens.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"47"},"PeriodicalIF":2.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistin as a potential diagnostic biomarker for sepsis: insights from DIA and ELISA analyses.","authors":"Youyu Lan, Wentao Guo, Wenhao Chen, Muhu Chen, Shaolan Li","doi":"10.1186/s12014-024-09498-1","DOIUrl":"10.1186/s12014-024-09498-1","url":null,"abstract":"<p><strong>Purpose: </strong>The primary objective of this investigation is to systematically screen and identify differentially expressed proteins (DEPs) within the plasma of individuals afflicted with sepsis. This endeavor employs both Data-Independent Acquisition (DIA) and enzyme-linked immunosorbent assay (ELISA) methodologies. The overarching goal is to furnish accessible and precise serum biomarkers conducive to the diagnostic discernment of sepsis.</p><p><strong>Method: </strong>The study encompasses 53 sepsis patients admitted to the Affiliated Hospital of Southwest Medical University between January 2019 and December 2020, alongside a control cohort consisting of 16 individuals devoid of sepsis pathology. Subsequently, a subset comprising 10 randomly selected subjects from the control group and 22 from the sepsis group undergoes quantitative proteomic analysis via DIA. The acquired data undergoes Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses, facilitating the construction of a Protein-Protein Interaction (PPI) network to discern potential markers. Validation of core proteins is then accomplished through ELISA. Comparative analysis between the normal and sepsis groups ensues, characterized by Receiver Operating Characteristic (ROC) curve construction to evaluate diagnostic efficacy.</p><p><strong>Result: </strong>A total of 187 DEPs were identified through bioinformatic methodologies. Examination reveals their predominant involvement in biological processes such as wound healing, coagulation, and blood coagulation. Functional pathway analysis further elucidates their engagement in the complement pathway and malaria. Resistin emerges as a candidate plasma biomarker, subsequently validated through ELISA. Notably, the protein exhibits significantly elevated levels in the serum of sepsis patients compared to the normal control group. ROC curve analysis underscores the robust diagnostic capacity of these biomarkers for sepsis.</p><p><strong>Conclusion: </strong>Data-Independent Acquisition (DIA) and Enzyme-Linked Immunosorbent Assay (ELISA) show increased Resistin levels in sepsis patients, suggesting diagnostic potential, warranting further research.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"46"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early detection of breast cancer through the diagnosis of Nipple Aspirate Fluid (NAF).","authors":"Abhishek Pant, Ashish P Anjankar, Sandesh Shende, Archana Dhok, Roshan Kumar Jha, Anjali Vagga Manglaram","doi":"10.1186/s12014-024-09495-4","DOIUrl":"https://doi.org/10.1186/s12014-024-09495-4","url":null,"abstract":"<p><p>The development of breast cancer has been mainly reported in women who have reached the post-menopausal stage; therefore, it is the primary factor responsible for death amongst postmenopausal women. However, if treated on time it has shown a survival rate of 20 years in about two-thirds of women. Cases of breast cancer have also been reported in younger women and the leading cause in them is their lifestyle pattern or they may be carriers of high penetrance mutated genes. Premenopausal women who have breast cancer have been diagnosed with aggressive build-up of tumors and are therefore at more risk of loss of life. Mammography is an effective way to test for breast cancer in women after menopause but is not so effective for premenopausal women or younger females. Imaging techniques like contrast-enhanced MRI can up to some extent indicate the presence of a tumor but it cannot adequately differentiate between benign and malignant tumors. Although the 'omics' strategies continuing for the last 20 years have been helpful at the molecular level in enabling the characteristics and proper understanding of such tumors over long-term longitudinal monitoring. Classification, diagnosis, and prediction of the outcomes have been made through tissue and serum biomarkers but these also fail to diagnose the disease at an early stage. Considerably there is no adequate detection technique present globally that can help early detection and provide adequate specificity, safety, sensitivity, and convenience for the younger and premenopausal women, thereby it becomes necessary to take early measures and build efficient tools and techniques for the same. Through biopsies of nipple aspirate fluid (NAF) biomarker profiling can be performed. It is a naturally secreted fluid from the cells of epithelium found in the breast. Nowadays, home-based liquid biopsy collection kits are also available through which a routine check on breast health can be performed with the help of NAF. Herein, we will review the biomarker screening liquid biopsy, and the new emerging technologies for the examination of cancer at an early stage, especially in premenopausal women.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"45"},"PeriodicalIF":2.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling of prostate cancer reveals molecular signatures under antiandrogen treatment.","authors":"Yurun Huang, Guanglin Yang, Xinpeng Yao, Yue Fang, Qiliang Lin, Menghan Zhou, Yiping Yang, Qinggui Meng, Qingyun Zhang, Shan Wang","doi":"10.1186/s12014-024-09490-9","DOIUrl":"10.1186/s12014-024-09490-9","url":null,"abstract":"<p><strong>Background: </strong>Tumorigenesis and progression of prostate cancer (PCa) are indispensably dependent on androgen receptor (AR). Antiandrogen treatment is the principal preference for patients with advanced PCa. However, the molecular characteristics of PCa with antiandrogen intervention have not yet been fully uncovered.</p><p><strong>Methods: </strong>We first performed proteome analysis with 32 PCa tumor samples and 10 adjacent tissues using data-independent acquisition (DIA)- parallel accumulation serial fragmentation (PASEF) proteomics. Then label-free quantification (LFQ) mass spectrometry was employed to analyze protein profiles in LNCaP and PC3 cells.</p><p><strong>Results: </strong>M-type creatine kinase CKM and cartilage oligomeric matrix protein COMP were demonstrated to have the potential to be diagnostic biomarkers for PCa at both mRNA and protein levels. Several E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) were significantly altered in PCa and PCa cells under enzalutamide treatment, and these proteins might reprogram proteostasis at protein levels in PCa. Finally, we discovered 127 significantly varied proteins in PCa samples with antiandrogen therapy and further uncovered 4 proteins in LNCaP cells upon enzalutamide treatment.</p><p><strong>Conclusions: </strong>Our research reveals new potential diagnostic biomarkers for prostate cancer and might help resensitize resistance to antiandrogen therapy.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"44"},"PeriodicalIF":2.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11202386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontiers in plasma proteome profiling platforms: innovations and applications.","authors":"Rajesh Kumar Soni","doi":"10.1186/s12014-024-09497-2","DOIUrl":"10.1186/s12014-024-09497-2","url":null,"abstract":"<p><p>Biomarkers play a crucial role in advancing precision medicine by enabling more targeted and individualized approaches to diagnosis and treatment. Various biofluids, including serum, plasma, cerebrospinal fluid (CSF), saliva, tears, pancreatic cyst fluids, and urine, have been identified as rich sources of potential for the early detection of disease biomarkers in conditions such as cancer, cardiovascular diseases, and neurodegenerative disorders. The analysis of plasma and serum in proteomics research encounters challenges due to their high complexity and the wide dynamic range of protein abundance. These factors impede the sensitivity, coverage, and precision of protein detection when employing mass spectrometry, a widely utilized technology in discovery proteomics. Conventional approaches such as Neat Plasma workflow are inefficient in accurately quantifying low-abundant proteins, including those associated with tissue leakage, immune response molecules, interleukins, cytokines, and interferons. Moreover, the manual nature of the workflow poses a significant hurdle in conducting large cohort studies. In this study, our focus is on comparing workflows for plasma proteomic profiling to establish a methodology that is not only sensitive and reproducible but also applicable for large cohort studies in biomarker discovery. Our investigation revealed that the Proteograph XT workflow outperforms other workflows in terms of plasma proteome depth, quantitative accuracy, and reproducibility while offering complete automation of sample preparation. Notably, Proteograph XT demonstrates versatility by applying it to various types of biofluids. Additionally, the proteins quantified widely cover secretory proteins in peripheral blood, and the pathway analysis enriched with relevant components such as interleukins, tissue necrosis factors, chemokines, and B and T cell receptors provides valuable insights. These proteins, often challenging to quantify in complex biological samples, hold potential as early detection markers for various diseases, thereby contributing to the improvement of patient care quality.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"43"},"PeriodicalIF":2.8,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of brain-enriched proteins in CSF as biomarkers of relapsing remitting multiple sclerosis.","authors":"Lincoln I Wurtz, Evdokiya Knyazhanskaya, Dorsa Sohaei, Ioannis Prassas, Sean Pittock, Maria Alice V Willrich, Ruba Saadeh, Ruchi Gupta, Hunter J Atkinson, Diane Grill, Martin Stengelin, Simon Thebault, Mark S Freedman, Eleftherios P Diamandis, Isobel A Scarisbrick","doi":"10.1186/s12014-024-09494-5","DOIUrl":"10.1186/s12014-024-09494-5","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a clinically and biologically heterogenous disease with currently unpredictable progression and relapse. After the development and success of neurofilament as a cerebrospinal fluid (CSF) biomarker, there is reinvigorated interest in identifying other markers of or contributors to disease. The objective of this study is to probe the predictive potential of a panel of brain-enriched proteins on MS disease progression and subtype.</p><p><strong>Methods: </strong>This study includes 40 individuals with MS and 14 headache controls. The MS cohort consists of 20 relapsing remitting (RR) and 20 primary progressive (PP) patients. The CSF of all individuals was analyzed for 63 brain enriched proteins using a method of liquid-chromatography tandem mass spectrometry. Wilcoxon rank sum test, Kruskal-Wallis one-way ANOVA, logistic regression, and Pearson correlation were used to refine the list of candidates by comparing relative protein concentrations as well as relation to known imaging and molecular biomarkers.</p><p><strong>Results: </strong>We report 30 proteins with some relevance to disease, clinical subtype, or severity. Strikingly, we observed widespread protein depletion in the disease CSF as compared to control. We identified numerous markers of relapsing disease, including KLK6 (kallikrein 6, OR = 0.367, p < 0.05), which may be driven by active disease as defined by MRI enhancing lesions. Other oligodendrocyte-enriched proteins also appeared at reduced levels in relapsing disease, namely CNDP1 (carnosine dipeptidase 1), LINGO1 (leucine rich repeat and Immunoglobin-like domain-containing protein 1), MAG (myelin associated glycoprotein), and MOG (myelin oligodendrocyte glycoprotein). Finally, we identified three proteins-CNDP1, APLP1 (amyloid beta precursor like protein 1), and OLFM1 (olfactomedin 1)-that were statistically different in relapsing vs. progressive disease raising the potential for use as an early biomarker to discriminate clinical subtype.</p><p><strong>Conclusions: </strong>We illustrate the utility of targeted mass spectrometry in generating potential targets for future biomarker studies and highlight reductions in brain-enriched proteins as markers of the relapsing remitting disease stage.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"42"},"PeriodicalIF":3.8,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glial fibrillary acidic protein, neurofilament light, matrix metalloprotease 3 and fatty acid binding protein 4 as non-invasive brain tumor biomarkers.","authors":"Atefeh Ghorbani, Miyo K Chatanaka, Lisa M Avery, Mingyue Wang, Jermaine Brown, Rachel Cohen, Taron Gorham, Salvia Misaghian, Nikhil Padmanabhan, Daniel Romero, Martin Stengelin, Anu Mathew, George Sigal, Jacob Wohlstadter, Craig Horbinski, Katy McCortney, Wei Xu, Gelareh Zadeh, Alireza Mansouri, George M Yousef, Eleftherios P Diamandis, Ioannis Prassas","doi":"10.1186/s12014-024-09492-7","DOIUrl":"10.1186/s12014-024-09492-7","url":null,"abstract":"<p><strong>Background: </strong>Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival.</p><p><strong>Methods: </strong>Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays.</p><p><strong>Results: </strong>High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas.</p><p><strong>Conclusions: </strong>GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.</p>","PeriodicalId":10468,"journal":{"name":"Clinical proteomics","volume":"21 1","pages":"41"},"PeriodicalIF":3.8,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}