Pub Date : 2024-03-01Epub Date: 2023-09-19DOI: 10.1002/prca.202300010
Shuang Yang, Chengbin Zhou, Lei Zhang, Yueting Xiong, Yongtao Zheng, Liuguan Bian, Xiaohui Liu
Purpose: Despite recent advancements in our understanding of driver gene mutations and heterogeneity within brain tumors, whether primary or metastatic (also known as secondary), our comprehension of proteomic changes remains inadequate. The aim of this study is to provide an informative source for brain tumor researches, and distinguish primary brain tumors and secondary brain tumors from extracranial origins based on proteomic analysis.
Experimental design: We assembled the most frequent brain tumors as follows: gliomas from WHO grade 2 to 4, with IDH1 mutations and wildtypes; brain metastases (BrMs) originating from lung cancer (LC), breast cancer (BC), ovarian cancer (OC), and colorectal cancer (CC). A total of 29 tissue samples were analyzed by label free quantitative mass spectrometry-based proteomics.
Results: In total, 8165 protein groups were quantified, of which 4383 proteins were filtered at 50% valid intensity values for downstream analysis. Proteomic analysis of BrMs reveals conserved features shared among multiple origins. While proteomic heterogeneities were found for discriminating different grades of gliomas, as well as IDH1 mutant and wildtype gliomas. In addition, notable distinctions were observed at the pathway level between BrMs and gliomas. Specifically, BrMs exhibited characteristic pathways focused on proliferation and immunomodulation after colonizing the brain, whereas gliomas primarily engaged in invasion processes.
Conclusions and clinical relevance: We characterized an extensive proteomic landscape of BrMs and gliomas. These findings have promising implications for the development of targeted therapies for BrMs and gliomas.
{"title":"Proteomic landscape of primary and metastatic brain tumors for heterogeneity discovery.","authors":"Shuang Yang, Chengbin Zhou, Lei Zhang, Yueting Xiong, Yongtao Zheng, Liuguan Bian, Xiaohui Liu","doi":"10.1002/prca.202300010","DOIUrl":"10.1002/prca.202300010","url":null,"abstract":"<p><strong>Purpose: </strong>Despite recent advancements in our understanding of driver gene mutations and heterogeneity within brain tumors, whether primary or metastatic (also known as secondary), our comprehension of proteomic changes remains inadequate. The aim of this study is to provide an informative source for brain tumor researches, and distinguish primary brain tumors and secondary brain tumors from extracranial origins based on proteomic analysis.</p><p><strong>Experimental design: </strong>We assembled the most frequent brain tumors as follows: gliomas from WHO grade 2 to 4, with IDH1 mutations and wildtypes; brain metastases (BrMs) originating from lung cancer (LC), breast cancer (BC), ovarian cancer (OC), and colorectal cancer (CC). A total of 29 tissue samples were analyzed by label free quantitative mass spectrometry-based proteomics.</p><p><strong>Results: </strong>In total, 8165 protein groups were quantified, of which 4383 proteins were filtered at 50% valid intensity values for downstream analysis. Proteomic analysis of BrMs reveals conserved features shared among multiple origins. While proteomic heterogeneities were found for discriminating different grades of gliomas, as well as IDH1 mutant and wildtype gliomas. In addition, notable distinctions were observed at the pathway level between BrMs and gliomas. Specifically, BrMs exhibited characteristic pathways focused on proliferation and immunomodulation after colonizing the brain, whereas gliomas primarily engaged in invasion processes.</p><p><strong>Conclusions and clinical relevance: </strong>We characterized an extensive proteomic landscape of BrMs and gliomas. These findings have promising implications for the development of targeted therapies for BrMs and gliomas.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300010"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150294","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}
Pub Date : 2024-01-01Epub Date: 2023-08-31DOI: 10.1002/prca.202300006
Shawn J Rice, Chandra P Belani
Purpose: Plasma is an abundant source of protein biomarkers. Mass spectrometry (MS) is an effective means to measure a large number of proteins in a single run. The recent development of data-independent acquisition with parallel accumulation and serial fragmentation (diaPASEF) on a trapped ion mobility spectrometer (TIMS) affords deep proteomic coverage with short liquid chromatography gradients. In this work, we utilized a process optimization approach, design of experiments (DoE), to maximize precursor identification for a plasma proteomic diaPASEF workflow.
Experimental design: A partial factorial design was used to screen 11 sample preparation factors and six diaPASEF MS acquisition factors. Selected factors were optimized using the response surface method.
Results: Three important sample preparation factors and the two important MS acquisition factors were identified in the screening experiments and were selected for separate optimization experiments. The optimal parameters were compared to our standard plasma proteomics workflows using either a 1-h or overnight trypsin digestion. The optimized method outperformed the 1-h digestion, and it was similar in performance to the overnight digestion, however, the optimized method could be completed in a day.
Conclusion and clinical relevance: We have used DoE to report an optimized plasma proteomics workflow for diaPASEF, however, established methods are already highly optimized, and resources may be better spent on running samples than comprehensive optimization.
目的:血浆是蛋白质生物标记物的丰富来源。质谱法(MS)是一次性测量大量蛋白质的有效方法。最近在困离子迁移率质谱仪(TIMS)上开发的独立于数据的并行累积和串行碎片采集(diaPASEF)技术,可在短液相色谱梯度下实现深度蛋白质组覆盖。在这项工作中,我们采用了一种流程优化方法--实验设计(DoE),以最大限度地鉴定血浆蛋白质组 diaPASEF 工作流程的前体:实验设计:采用部分因子设计筛选 11 个样品制备因子和 6 个 diaPASEF MS 采集因子。实验设计:采用部分因子设计筛选了 11 个样品制备因子和 6 个 diaPASEF MS 采集因子,并采用响应面法对所选因子进行了优化:结果:在筛选实验中确定了三个重要的样品制备因素和两个重要的质谱采集因素,并分别进行了优化实验。优化参数与我们使用 1 小时或过夜胰蛋白酶消化的标准血浆蛋白质组学工作流程进行了比较。优化后的方法优于1小时消化法,与过夜消化法性能相似,但优化后的方法可在一天内完成:我们利用 DoE 报告了 diaPASEF 的优化血浆蛋白质组学工作流程,然而,已有的方法已经高度优化,与其进行全面优化,不如将资源花在运行样本上。
{"title":"Design of experiments approach for systematic optimization of a single-shot diaPASEF plasma proteomics workflow applicable for high-throughput.","authors":"Shawn J Rice, Chandra P Belani","doi":"10.1002/prca.202300006","DOIUrl":"10.1002/prca.202300006","url":null,"abstract":"<p><strong>Purpose: </strong>Plasma is an abundant source of protein biomarkers. Mass spectrometry (MS) is an effective means to measure a large number of proteins in a single run. The recent development of data-independent acquisition with parallel accumulation and serial fragmentation (diaPASEF) on a trapped ion mobility spectrometer (TIMS) affords deep proteomic coverage with short liquid chromatography gradients. In this work, we utilized a process optimization approach, design of experiments (DoE), to maximize precursor identification for a plasma proteomic diaPASEF workflow.</p><p><strong>Experimental design: </strong>A partial factorial design was used to screen 11 sample preparation factors and six diaPASEF MS acquisition factors. Selected factors were optimized using the response surface method.</p><p><strong>Results: </strong>Three important sample preparation factors and the two important MS acquisition factors were identified in the screening experiments and were selected for separate optimization experiments. The optimal parameters were compared to our standard plasma proteomics workflows using either a 1-h or overnight trypsin digestion. The optimized method outperformed the 1-h digestion, and it was similar in performance to the overnight digestion, however, the optimized method could be completed in a day.</p><p><strong>Conclusion and clinical relevance: </strong>We have used DoE to report an optimized plasma proteomics workflow for diaPASEF, however, established methods are already highly optimized, and resources may be better spent on running samples than comprehensive optimization.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300006"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119351","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}
Purpose: This research aimed to find potential HER2 mutations that would have an impact on breast cancer and investigate the underlying mechanism.
Experimental design: This study first investigated 238 pairs of breast cancer and para-cancerous tissue samples from patients on the targeted next-generation sequencing (tNGS) platform. CCK-8 and clone formation assay were used to investigate whether the mutation exerts proliferative effects on breast cancer cells. In addition, mass spectrometry-based comparative proteomic and phosphoproteomic analyses of the mutation types and wild types of MCF-7 cell lines were carried out.
Results: Among the identified mutations, a new mutation HER2 L796P promoted the proliferation of breast cancer cells and had resistance to lapatinib using CCK-8 cell proliferation assay and clone formation assay. The bioinformatic analysis showed that RAS family proteins and ERK phosphorylated proteins significantly increased in the L796P mutant cells. The Gene Ontology (GO) analysis revealed that L796P mutation affected the function of breast cancer at the level of upstream genes in the MAPK and PI3K-AKT-TOR pathways.
Conclusions and clinical relevance: This study demonstrated that a rare mutation HER2 L796P could be a potential therapeutic target for the clinical management of breast cancer.
{"title":"Rare HER2 L796P missense mutation promotes the growth and oncogenic signaling in breast cancer cells.","authors":"Dongxue Zhang, Xiaoyu Shi, Weimin Zheng, Xian Zhang, Yun Chen","doi":"10.1002/prca.202300061","DOIUrl":"10.1002/prca.202300061","url":null,"abstract":"<p><strong>Purpose: </strong>This research aimed to find potential HER2 mutations that would have an impact on breast cancer and investigate the underlying mechanism.</p><p><strong>Experimental design: </strong>This study first investigated 238 pairs of breast cancer and para-cancerous tissue samples from patients on the targeted next-generation sequencing (tNGS) platform. CCK-8 and clone formation assay were used to investigate whether the mutation exerts proliferative effects on breast cancer cells. In addition, mass spectrometry-based comparative proteomic and phosphoproteomic analyses of the mutation types and wild types of MCF-7 cell lines were carried out.</p><p><strong>Results: </strong>Among the identified mutations, a new mutation HER2 L796P promoted the proliferation of breast cancer cells and had resistance to lapatinib using CCK-8 cell proliferation assay and clone formation assay. The bioinformatic analysis showed that RAS family proteins and ERK phosphorylated proteins significantly increased in the L796P mutant cells. The Gene Ontology (GO) analysis revealed that L796P mutation affected the function of breast cancer at the level of upstream genes in the MAPK and PI3K-AKT-TOR pathways.</p><p><strong>Conclusions and clinical relevance: </strong>This study demonstrated that a rare mutation HER2 L796P could be a potential therapeutic target for the clinical management of breast cancer.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300061"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10170719","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}
Pub Date : 2024-01-01Epub Date: 2023-09-06DOI: 10.1002/prca.202300015
Junyu Chen, Qin Hui, Chang Liu, Jaysingh Brijkumar, Johnathan A Edwards, Claudia E Ordóñez, Mathew R Dudgeon, Henry Sunpath, Selvan Pillay, Pravi Moodley, Daniel R Kuritzkes, Mohamed Y S Moosa, Tooru Nemoto, Vincent C Marconi, Yan V Sun
Purpose: Elevated levels of inflammation associated with human immunodeficiency virus (HIV) infection are one of the primary causes for the burden of age-related diseases among people with HIV (PWH). Circulating proteins can be used to investigate pathways to inflammation among PWH.
Experimental design: We profiled 73 inflammation-related protein markers and assessed their associations with chronological age, sex, and CD4+ cell count among 87 black South African PWH before antiretroviral therapy (ART).
Results: We identified 1, 1, and 14 inflammatory proteins significantly associated with sex, CD4+ cell count, and age respectively. Twelve out of 14 age-associated proteins have been reported to be associated with age in the general population, and 4 have previously shown significant associations with age for PWH. Furthermore, many of the age-associated proteins such as CST5, CCL23, SLAMF1, MMP-1, MCP-1, and CDCP1 have been linked to chronic diseases such as cardiovascular disease and neurocognitive decline in the general population. We also found a synergistic interaction between male and older age accounting for excessive expression of CST5.
Conclusions and clinical relevance: We found that advanced age may lead to the elevation of multiple inflammatory proteins among PWH. We also demonstrated the potential utility of proteomics for evaluating and characterizing the inflammatory status of PWH.
{"title":"Associations of inflammation-related proteome with demographic and clinical characteristics of people with HIV in South Africa.","authors":"Junyu Chen, Qin Hui, Chang Liu, Jaysingh Brijkumar, Johnathan A Edwards, Claudia E Ordóñez, Mathew R Dudgeon, Henry Sunpath, Selvan Pillay, Pravi Moodley, Daniel R Kuritzkes, Mohamed Y S Moosa, Tooru Nemoto, Vincent C Marconi, Yan V Sun","doi":"10.1002/prca.202300015","DOIUrl":"10.1002/prca.202300015","url":null,"abstract":"<p><strong>Purpose: </strong>Elevated levels of inflammation associated with human immunodeficiency virus (HIV) infection are one of the primary causes for the burden of age-related diseases among people with HIV (PWH). Circulating proteins can be used to investigate pathways to inflammation among PWH.</p><p><strong>Experimental design: </strong>We profiled 73 inflammation-related protein markers and assessed their associations with chronological age, sex, and CD4<sup>+</sup> cell count among 87 black South African PWH before antiretroviral therapy (ART).</p><p><strong>Results: </strong>We identified 1, 1, and 14 inflammatory proteins significantly associated with sex, CD4<sup>+</sup> cell count, and age respectively. Twelve out of 14 age-associated proteins have been reported to be associated with age in the general population, and 4 have previously shown significant associations with age for PWH. Furthermore, many of the age-associated proteins such as CST5, CCL23, SLAMF1, MMP-1, MCP-1, and CDCP1 have been linked to chronic diseases such as cardiovascular disease and neurocognitive decline in the general population. We also found a synergistic interaction between male and older age accounting for excessive expression of CST5.</p><p><strong>Conclusions and clinical relevance: </strong>We found that advanced age may lead to the elevation of multiple inflammatory proteins among PWH. We also demonstrated the potential utility of proteomics for evaluating and characterizing the inflammatory status of PWH.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300015"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177819","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}
Pub Date : 2024-01-01Epub Date: 2023-06-17DOI: 10.1002/prca.202300008
Patricia Sosa-Acosta, Geisa P C Evaristo, Joseph A M Evaristo, Gabriel Reis Alves Carneiro, Mauricio Quiñones-Vega, Gustavo Monnerat, Adriana Melo, Patrícia P Garcez, Fábio C S Nogueira, Gilberto B Domont
Purpose: Our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)-infected patients and their relation to congenital Zika syndrome (CZS) progression.
Experimental design: We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses.
Results: Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities.
Conclusions and clinical relevance: This study enhances our understanding of the development of CZS pathology and sheds light on dysregulated pathways that could be relevant for future studies.
{"title":"Amniotic fluid metabolomics identifies impairment of glycerophospholipid and amino acid metabolism during congenital Zika syndrome development.","authors":"Patricia Sosa-Acosta, Geisa P C Evaristo, Joseph A M Evaristo, Gabriel Reis Alves Carneiro, Mauricio Quiñones-Vega, Gustavo Monnerat, Adriana Melo, Patrícia P Garcez, Fábio C S Nogueira, Gilberto B Domont","doi":"10.1002/prca.202300008","DOIUrl":"10.1002/prca.202300008","url":null,"abstract":"<p><strong>Purpose: </strong>Our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)-infected patients and their relation to congenital Zika syndrome (CZS) progression.</p><p><strong>Experimental design: </strong>We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses.</p><p><strong>Results: </strong>Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities.</p><p><strong>Conclusions and clinical relevance: </strong>This study enhances our understanding of the development of CZS pathology and sheds light on dysregulated pathways that could be relevant for future studies.</p>","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e2300008"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9697157","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}
Purpose: 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.
Experimental design: 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.
Results: 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.
Conclusions and clinical relevance: 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.
{"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}
Background: 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.
Methods: 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.
Results: 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.
Conclusion and clinical relevance: 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.
{"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}
Pub Date : 2023-11-01Epub Date: 2023-06-07DOI: 10.1002/prca.202200109
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
Purpose: 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).
Experimental design: 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).
Results: 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).
Conclusion and clinical relevance: Our findings suggest the potential of the protein VCP as biomarker in prognostication prediction in pediatric AML.
{"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}
Pub Date : 2023-11-01Epub Date: 2023-08-02DOI: 10.1002/prca.202200116
Mirella Luciani, Ivanka Krasteva, Tiziana Di Febo, Fabrizia Perletta, Federica D'Onofrio, Fabrizio De Massis, Nicola D'Alterio, Flavio Sacchini, Manuela Tittarelli
Purpose: 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.
Experimental design: 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.
Results: 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.
Conclusions and clinical relevance: 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.
{"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}
Pub Date : 2023-11-01Epub Date: 2023-05-31DOI: 10.1002/prca.202300016
Rama N Behera, Vinod S Bisht, Kuldeep Giri, Kiran Ambatipudi
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.
{"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}