{"title":"Cerebrospinal fluid proteins in idiopathic intracranial hypertension: An exploratory SWATH proteomics analysis.","authors":"Awadh Kishor Pandit, Shubham Misra, Shantanu Sengupta, Rahul Chakraborty, Praveen Singh, Gyaninder Pal Singh, Swati Phuljhele, Achal K Srivastava, Deepti Vibha, Ajay Garg, Vivek Shankar, Dheeraj Mohania, Garima Shukla, Kameshwar Prasad","doi":"10.1002/prca.202300021","DOIUrl":"10.1002/prca.202300021","url":null,"abstract":"<p><strong>Purpose: </strong>The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases compared to controls using SWATH-MS proteomics approach.</p><p><strong>Experimental design: </strong>CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change > 1.5 or < 0.67 and p-value < 0.05 were considered significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD027751. Statistical analysis was conducted in R version 3.6.2.</p><p><strong>Results: </strong>We included CSF samples from 33 subjects, consisting of 13 IIH cases and 20 controls. A total of 262 proteins were identified in Proteinpilot search. Through SWATH analysis, we quantified 232 proteins. We observed 37 differentially expressed proteins between the two groups with 24 upregulated and 13 downregulated proteins. There were two differential proteins among overweight versus non-overweight IIH cases. Network for 23 proteins was highly connected in the interaction analysis.</p><p><strong>Conclusions and clinical relevance: </strong>Neurosecretory, neuroendocrine, and inflammatory proteins were predominantly involved in causing IIH. This exploratory study served as a platform to identify 37 differentially expressed proteins in IIH and also showed significant differences between overweight and non-overweight IIH patients.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300021"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10310685","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":"LC-MS-based urine metabolomics analysis of chronic subdural hematoma for biomarker discovery.","authors":"Jiameng Sun, Yunwei Ou, Xiaoyan Liu, Haidan Sun, Zhengguang Guo, Feng Qi, Ying Lan, Weiming Liu, Wei Sun","doi":"10.1002/prca.202200107","DOIUrl":"10.1002/prca.202200107","url":null,"abstract":"<p><strong>Background: </strong>Chronic subdural hematoma (CSDH) is one of the most common neurosurgical diseases with atypical manifestations. The aim of this study was to utilize urine metabolomics to explore potential biomarkers for the diagnosis and prognosis of CSDH.</p><p><strong>Methods: </strong>Seventy-seven healthy controls and ninety-two patients with CSDH were enrolled in our study. In total, 261 urine samples divided into the discovery group and validation group were analyzed by LC-MS. The statistical analysis and functional annotation were applied to discover potential biomarker panels and altered metabolic pathways.</p><p><strong>Results: </strong>A total of 53 differential metabolites were identified in this study. And the urinary metabolic profiles showed apparent separation between patients and controls. Further functional annotation showed that the differential metabolites were associated with lipid metabolism, fatty acid metabolism, amino acid metabolism, biotin metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions. Moreover, one panel of Capryloylglycine, cis-5-Octenoic acid, Ethisterone, and 5,6-DiHETE showed good predictive performance in the diagnosis of CSDH, with an AUC of 0.89 in discovery group and an AUC of 0.822 in validation group. Another five metabolites (Trilobinol, 3'-Hydroxyropivacaine, Ethisterone, Arginyl-Proline, 5-alpha-Dihydrotestosterone glucuronide) showed the levels of them returned to a healthy state after surgery, showing good possibility to monitor the recovery of CSDH patients.</p><p><strong>Conclusion and clinical relevance: </strong>The findings of the study revealed urine metabolomic differences between CSDH and controls. The potentially diagnostic and prognostic biomarker panels of urine metabolites were established, and functional analysis demonstrated deeper metabolic disorders of CSDH, which might conduce to improve early diagnose of CSDH clinically.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2200107"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268310","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}
Fieke W Hoff, Yihua Qiu, Brandon D Brown, Robert B Gerbing, Amanda R Leonti, Rhonda E Ries, Alan S Gamis, Richard Aplenc, Edward Anders Kolb, Todd A Alonzo, Soheil Meshinchi, Gaye N Jenkins, Terzah M Horton, Steven M Kornblau
{"title":"Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.","authors":"Fieke W Hoff, Yihua Qiu, Brandon D Brown, Robert B Gerbing, Amanda R Leonti, Rhonda E Ries, Alan S Gamis, Richard Aplenc, Edward Anders Kolb, Todd A Alonzo, Soheil Meshinchi, Gaye N Jenkins, Terzah M Horton, Steven M Kornblau","doi":"10.1002/prca.202200109","DOIUrl":"10.1002/prca.202200109","url":null,"abstract":"<p><strong>Purpose: </strong>The endoplasmic reticulum (ER) is the major site of protein synthesis and folding in the cell. ER-associated degradation (ERAD) and unfolded protein response (UPR) are the main mechanisms of ER-mediated cell stress adaptation. Targeting the cell stress response is a promising therapeutic approach in acute myeloid leukemia (AML).</p><p><strong>Experimental design: </strong>Protein expression levels of valosin-containing protein (VCP), a chief element of ERAD, were measured in peripheral blood samples from in 483 pediatric AML patients using reverse phase protein array methodology. Patients participated in the Children's Oncology Group AAML1031 phase 3 clinical trial that randomized patients to standard chemotherapy (cytarabine (Ara-C), daunorubicin, and etoposide [ADE]) versus ADE plus bortezomib (ADE+BTZ).</p><p><strong>Results: </strong>Low-VCP expression was significantly associated with favorable 5-year overall survival (OS) rate compared to middle-high-VCP expression (81% versus 63%, p < 0.001), independent of additional bortezomib treatment. Multivariable Cox regression analysis identified VCP as independent predictor of clinical outcome. UPR proteins IRE1 and GRP78 had significant negative correlation with VCP. Five-year OS in patients characterized by low-VCP, moderately high-IRE1 and high-GRP78 improved after treatment with ADE+BTZ versus ADE (66% versus 88%, p = 0.026).</p><p><strong>Conclusion and clinical relevance: </strong>Our findings suggest the potential of the protein VCP as biomarker in prognostication prediction in pediatric AML.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2200109"},"PeriodicalIF":2.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10700663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9626786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirella Luciani, Ivanka Krasteva, Tiziana Di Febo, Fabrizia Perletta, Federica D'Onofrio, Fabrizio De Massis, Nicola D'Alterio, Flavio Sacchini, Manuela Tittarelli
{"title":"Proteomics and bioinformatics investigations to improve serological diagnosis of canine brucellosis.","authors":"Mirella Luciani, Ivanka Krasteva, Tiziana Di Febo, Fabrizia Perletta, Federica D'Onofrio, Fabrizio De Massis, Nicola D'Alterio, Flavio Sacchini, Manuela Tittarelli","doi":"10.1002/prca.202200116","DOIUrl":"10.1002/prca.202200116","url":null,"abstract":"<p><strong>Purpose: </strong>Brucella canis is pathogenic for dogs and humans. Serological diagnosis is a cost-effective approach for disease surveillance, but a major drawback of current serological tests is the cross-reactivity with other bacteria that results in false positive reactions. Development of indirect tests with improved sensitivity and specificity that use selected B. canis proteins instead of the whole antigen remain a priority.</p><p><strong>Experimental design: </strong>A western blotting assay was developed to define the serum antibody patterns associated to infection using a panel of positive and negative dog sera. B. canis positive sera recognized immunogenic bands ranging from 7 to 30 kDa that were then submitted to ESI-LC-MS/MS and analyzed by bioinformatics tools.</p><p><strong>Results: </strong>A total of 398 B. canis proteins were identified. Bioinformatics tools identified 16 non cytoplasmic immunogenic proteins predicted as non-homologous with the most important Brucella cross-reactive bacteria and nine B. canis proteins non-homologous to B. ovis; among the latter, one resulted non-homologous to B. melitensis. Data are available via ProteomeXchange with identifier PXD042682.</p><p><strong>Conclusions and clinical relevance: </strong>The western blotting test developed was able to distinguish between infected and non-infected animals and may serve as a confirmatory test for the serological diagnosis of B. canis. The mass spectrometry and in silico results lead to the identification of specific candidate antigens that pave the way for the development of more accurate indirect diagnostic tests.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2200116"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9927263","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}
Rama N Behera, Vinod S Bisht, Kuldeep Giri, Kiran Ambatipudi
{"title":"Realm of proteomics in breast cancer management and drug repurposing to alleviate intricacies of treatment.","authors":"Rama N Behera, Vinod S Bisht, Kuldeep Giri, Kiran Ambatipudi","doi":"10.1002/prca.202300016","DOIUrl":"10.1002/prca.202300016","url":null,"abstract":"<p><p>Breast cancer, a multi-networking heterogeneous disease, has emerged as a serious impediment to progress in clinical oncology. Although technological advancements and emerging cancer research studies have mitigated breast cancer lethality, a precision cancer-oriented solution has not been achieved. Thus, this review will persuade the acquiescence of proteomics-based diagnostic and therapeutic options in breast cancer management. Recently, the evidence of breast cancer health surveillance through imaging proteomics, single-cell proteomics, interactomics, and post-translational modification (PTM) tracking, to construct proteome maps and proteotyping for stage-specific and sample-specific cancer subtyping have outperformed conventional ways of dealing with breast cancer by increasing diagnostic efficiency, prognostic value, and predictive response. Additionally, the paradigm shift in applied proteomics for designing a chemotherapy regimen to identify novel drug targets with minor adverse effects has been elaborated. Finally, the potential of proteomics in alleviating the occurrence of chemoresistance and enhancing reprofiled drugs' effectiveness to combat therapeutic obstacles has been discussed. Owing to the enormous potential of proteomics techniques, the clinical recognition of proteomics in breast cancer management can be achievable and therapeutic intricacies can be surmountable.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300016"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9606883","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":"The functional roles of m6A modification in prostate cancer.","authors":"Fa Zhang, Feng Chen, Chao Wang, Feng-Hai Zhou","doi":"10.1002/prca.202200108","DOIUrl":"10.1002/prca.202200108","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the most prevalent malignancy of the male genitourinary system, and its etiology suggests that genetics is an essential risk factor for its development and progression, while exogenous factors may have an significant impact on this risk. Initial diagnosis of advanced PCa is relatively frequent, and androgen deprivation therapy (ADT) is the predominant standard of care for PCa and the basis for various novel combination therapy regimens, and is often required throughout the patient's subsequent treatment. Although diagnostic modalities and treatment options are evolving, some patients suffer from complications, including biochemical relapse, metastasis and treatment resistance. Mechanisms of PCa pathogenesis and progression have been the focus of research. N6-methyladenosine (m6A) is an RNA modification involved in cell physiology and tumor metabolism. It has been observed to affect the evolution of diverse cancers through the regulation of gene expression. Genes associated with m6A are prominent in PCa and are involved in multiple aspects of desmoresistant PCa occurrence, progression, PCa bone metastasis (BM), and treatment resistance. Here, we explore the role of m6A modifications in promoting PCa.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2200108"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9687989","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}
Carlo Brogna, Simone Cristoni, Giuliano Marino, Luigi Montano, Valentina Viduto, Mark Fabrowski, Gennaro Lettieri, Marina Piscopo
{"title":"Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS-CoV-2: Possible molecular mechanisms.","authors":"Carlo Brogna, Simone Cristoni, Giuliano Marino, Luigi Montano, Valentina Viduto, Mark Fabrowski, Gennaro Lettieri, Marina Piscopo","doi":"10.1002/prca.202300048","DOIUrl":"10.1002/prca.202300048","url":null,"abstract":"<p><strong>Purpose: </strong>The SARS-CoV-2 pandemic prompted the development and use of next-generation vaccines. Among these, mRNA-based vaccines consist of injectable solutions of mRNA encoding for a recombinant Spike, which is distinguishable from the wild-type protein due to specific amino acid variations introduced to maintain the protein in a prefused state. This work presents a proteomic approach to reveal the presence of recombinant Spike protein in vaccinated subjects regardless of antibody titer.</p><p><strong>Experimental design: </strong>Mass spectrometry examination of biological samples was used to detect the presence of specific fragments of recombinant Spike protein in subjects who received mRNA-based vaccines.</p><p><strong>Results: </strong>The specific PP-Spike fragment was found in 50% of the biological samples analyzed, and its presence was independent of the SARS-CoV-2 IgG antibody titer. The minimum and maximum time at which PP-Spike was detected after vaccination was 69 and 187 days, respectively.</p><p><strong>Conclusions and clinical relevance: </strong>The presented method allows to evaluate the half-life of the Spike protein molecule \"PP\" and to consider the risks or benefits in continuing to administer additional booster doses of the SARS-CoV-2 mRNA vaccine. This approach is of valuable support to complement antibody level monitoring and represents the first proteomic detection of recombinant Spike in vaccinated subjects.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300048"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10477408","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":"Identification of a potential prognostic plasma biomarker of acute ischemic stroke via untargeted LC-MS metabolomics.","authors":"Ming-Hsiu Wu, Chiz-Tzung Chang, Yu-Ning Lin, Chao-Jung Chen","doi":"10.1002/prca.202200081","DOIUrl":"10.1002/prca.202200081","url":null,"abstract":"<p><strong>Purpose: </strong>Stroke is the sudden death of brain cells in a localized area due to an inadequate blood flow or blood vessel rupture, and it seriously affects the quality of life. The metabolite biomarkers are needed for predicting the functional outcome of acute ischemic stroke (AIS).</p><p><strong>Experimental design: </strong>To identify biomarkers for AIS, untargeted LC/MS metabolomics was performed on plasma samples from subjects with favorable prognosis (mRS ≤ 2) and unfavorable prognosis (mRS > 2). The identified markers were further absolutely quantified by a targeted MRM approach.</p><p><strong>Results: </strong>There were 10 upregulated and 26 downregulated markers. Among these candidates, one was successfully identified as glycocholic acid and then absolutely quantified in plasma samples. Glycocholic acid could discriminate between subjects with favorable and unfavorable prognosis with an area under the curve (AUC) of 0.68 and odds ratio of 5.88.</p><p><strong>Conclusions and clinical relevance: </strong>Glycocholic acid was identified as a potential plasma metabolite marker of non-progressive outcomes after ischemic stroke and could serve as predictive prognostic markers for clinical acute stroke outcomes.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2200081"},"PeriodicalIF":2.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067661","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}