首页 > 最新文献

PROTEOMICS – Clinical Applications最新文献

英文 中文
Proteomic landscape of primary and metastatic brain tumors for heterogeneity discovery. 用于异质性发现的原发性和转移性脑肿瘤的蛋白质组学景观。
IF 2 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-03-01 Epub Date: 2023-09-19 DOI: 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.

目的:尽管我们对脑肿瘤中驱动基因突变和异质性的理解最近取得了进展,无论是原发性还是转移性(也称为继发性),但我们对蛋白质组学变化的理解仍然不足。本研究的目的是为脑肿瘤研究提供信息来源,并基于蛋白质组学分析区分原发性脑肿瘤和继发性脑肿瘤。实验设计:我们收集了最常见的脑肿瘤如下:世界卫生组织2至4级胶质瘤,IDH1突变和野生型;源于肺癌症(LC)、癌症(BC)、卵巢癌症(OC)和癌症(CC)的脑转移(BrMs)。通过基于蛋白质组学的无标记定量质谱分析,共分析了29个组织样本。结果:总共量化了8165个蛋白质组,其中4383个蛋白质以50%的有效强度值过滤,用于下游分析。BrMs的蛋白质组学分析揭示了多种来源之间共享的保守特征。而蛋白质组异质性被发现可以区分不同级别的胶质瘤,以及IDH1突变型和野生型胶质瘤。此外,在BrMs和胶质瘤之间的通路水平上观察到显著的差异。具体而言,BrMs在定植于大脑后表现出专注于增殖和免疫调节的特征性途径,而胶质瘤主要参与侵袭过程。结论和临床相关性:我们对脑胶质瘤和脑胶质瘤的广泛蛋白质组学景观进行了表征。这些发现对BrMs和神经胶质瘤靶向治疗的发展具有重要意义。
{"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}
引用次数: 0
Design of experiments approach for systematic optimization of a single-shot diaPASEF plasma proteomics workflow applicable for high-throughput. 用于系统优化适用于高通量的单次 diaPASEF 血浆蛋白质组学工作流程的实验设计方法。
IF 2 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-01-01 Epub Date: 2023-08-31 DOI: 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}
引用次数: 0
Rare HER2 L796P missense mutation promotes the growth and oncogenic signaling in breast cancer cells. 罕见的 HER2 L796P 错义突变促进了乳腺癌细胞的生长和致癌信号传导。
IF 2 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-01-01 Epub Date: 2023-09-06 DOI: 10.1002/prca.202300061
Dongxue Zhang, Xiaoyu Shi, Weimin Zheng, Xian Zhang, Yun Chen

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.

目的:本研究旨在寻找对乳腺癌有影响的潜在HER2突变,并研究其潜在机制:本研究首先在靶向新一代测序(tNGS)平台上检测了 238 对患者的乳腺癌和癌旁组织样本。通过CCK-8和克隆形成试验研究突变是否对乳腺癌细胞产生增殖作用。此外,还对突变类型和野生型 MCF-7 细胞系进行了基于质谱的比较蛋白质组学和磷酸蛋白质组学分析:结果:在已发现的突变中,一个新的突变 HER2 L796P 促进了乳腺癌细胞的增殖,并通过 CCK-8 细胞增殖试验和克隆形成试验对拉帕替尼产生了耐药性。生物信息学分析表明,L796P突变细胞中的RAS家族蛋白和ERK磷酸化蛋白明显增加。基因本体(GO)分析显示,L796P突变在MAPK和PI3K-AKT-TOR通路的上游基因水平上影响了乳腺癌的功能:本研究表明,罕见的 HER2 L796P 突变可能是乳腺癌临床治疗的潜在治疗靶点。
{"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}
引用次数: 0
Associations of inflammation-related proteome with demographic and clinical characteristics of people with HIV in South Africa. 炎症相关蛋白质组与南非艾滋病病毒感染者的人口和临床特征之间的关系。
IF 2 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-01-01 Epub Date: 2023-09-06 DOI: 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.

目的:与人类免疫缺陷病毒(HIV)感染相关的炎症水平升高是造成艾滋病病毒感染者(PWH)老年相关疾病负担的主要原因之一。循环蛋白可用于研究PWH的炎症途径:实验设计:我们对 87 名接受抗逆转录病毒疗法(ART)的南非黑人艾滋病病毒感染者的 73 种炎症相关蛋白标记物进行了分析,并评估了它们与年龄、性别和 CD4+ 细胞计数的关系:结果:我们发现分别有 1、1 和 14 种炎症蛋白与性别、CD4+细胞计数和年龄显著相关。据报道,在 14 种年龄相关蛋白中,有 12 种与普通人群的年龄有关,有 4 种曾显示与 PWH 患者的年龄有显著关联。此外,许多年龄相关蛋白,如 CST5、CCL23、SLAMF1、MMP-1、MCP-1 和 CDCP1 都与心血管疾病和神经认知功能下降等慢性疾病有关。我们还发现,男性和高龄之间存在协同作用,导致了 CST5 的过度表达:我们发现,高龄可能会导致 PWH 中多种炎症蛋白的升高。我们还证明了蛋白质组学在评估和描述 PWH 炎症状态方面的潜在作用。
{"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}
引用次数: 0
Amniotic fluid metabolomics identifies impairment of glycerophospholipid and amino acid metabolism during congenital Zika syndrome development. 羊水代谢组学确定了先天性寨卡综合征发育过程中甘油磷脂和氨基酸代谢的损伤。
IF 2 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-01-01 Epub Date: 2023-06-17 DOI: 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.

目的:我们的主要目标是确定寨卡病毒(ZIKV)感染患者羊水(AF)代谢组的改变及其与先天性寨卡综合征(CZS)进展的关系:实验设计:我们采用非靶向代谢组学策略分析了7名孕妇的AF:健康孕妇和感染寨卡病毒并怀有非小头畸形和小头畸形胎儿的孕妇:结果:感染者的特点是甘油磷脂代谢障碍,这在小头畸形中更为明显。AF 中甘油磷脂浓度的降低可能是细胞内脂类向胎盘或胎儿发育中的组织运输的结果。细胞内脂质浓度的升高可导致线粒体功能障碍和脂滴积聚引起的神经变性。此外,氨基酸代谢失调是小头畸形表型的分子指纹,特别是丝氨酸和脯氨酸代谢失调。这两种氨基酸的缺乏都与神经退行性疾病、宫内发育迟缓和胎盘异常有关:本研究加深了我们对CZS病理发展的理解,并揭示了可能与未来研究相关的失调途径。
{"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}
引用次数: 0
Cerebrospinal fluid proteins in idiopathic intracranial hypertension: An exploratory SWATH proteomics analysis. 特发性颅内高压的脑脊液蛋白质:探索性 SWATH 蛋白质组学分析
IF 2 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-01-01 Epub Date: 2023-08-07 DOI: 10.1002/prca.202300021
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

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.

目的:特发性颅内高压症(IIH)的发病机制目前尚不清楚。这项探索性研究旨在利用SWATH-MS蛋白质组学方法鉴定特发性颅内高压病例与对照组相比潜在的脑脊液(CSF)生物标志物:实验设计:前瞻性地收集IIH病例和对照组的脑脊液样本,并对其进行基于SWATH-MS的非靶向蛋白质组学分析。结果:33 例 IIH 病例的 CSF 样本中的蛋白质折叠变化大于 1.5:我们纳入了 33 例受试者的 CSF 样本,包括 13 例 IIH 病例和 20 例对照组。通过 Proteinpilot 搜索共鉴定出 262 个蛋白质。通过 SWATH 分析,我们量化了 232 个蛋白质。我们观察到两组之间有 37 个差异表达的蛋白质,其中 24 个上调,13 个下调。超重与非超重 IIH 病例中有两种蛋白质存在差异。在相互作用分析中,23种蛋白质的网络高度关联:神经分泌、神经内分泌和炎症蛋白是导致 IIH 的主要因素。这项探索性研究为确定 IIH 中 37 种差异表达的蛋白质提供了一个平台,同时还显示了超重和非超重 IIH 患者之间的显著差异。
{"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}
引用次数: 0
LC-MS-based urine metabolomics analysis of chronic subdural hematoma for biomarker discovery. 基于 LC-MS 的慢性硬膜下血肿尿液代谢组学分析用于生物标记物的发现。
IF 2 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-01-01 Epub Date: 2023-09-11 DOI: 10.1002/prca.202200107
Jiameng Sun, Yunwei Ou, Xiaoyan Liu, Haidan Sun, Zhengguang Guo, Feng Qi, Ying Lan, Weiming Liu, Wei Sun

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.

背景:慢性硬膜下血肿(CSDH)是表现不典型的最常见神经外科疾病之一。本研究旨在利用尿液代谢组学探索诊断和预后 CSDH 的潜在生物标志物:我们的研究共纳入了 77 名健康对照者和 92 名 CSDH 患者。共对 261 份尿液样本进行了 LC-MS 分析,分为发现组和验证组。通过统计分析和功能注释发现了潜在的生物标志物组和改变的代谢通路:结果:本研究共鉴定出 53 种差异代谢物。结果:本研究共鉴定出 53 种差异代谢物,患者和对照组的尿液代谢谱显示出明显的差异。进一步的功能注释显示,差异代谢物与脂质代谢、脂肪酸代谢、氨基酸代谢、生物素代谢、类固醇激素生物合成以及戊糖和葡萄糖醛酸的相互转化有关。此外,一个由辛酰甘氨酸、顺式-5-辛烯酸、乙甾酮和 5,6-DiHETE 组成的小组对 CSDH 的诊断具有良好的预测性,发现组的 AUC 为 0.89,验证组的 AUC 为 0.822。另外五种代谢物(曲洛比诺、3'-羟基丙哌卡因、乙甙甾酮、精氨酰-脯氨酸、5-α-二氢睾酮葡萄糖醛酸苷)的水平在术后恢复到健康状态,显示出监测CSDH患者恢复情况的良好可能性:研究结果显示了 CSDH 与对照组之间的尿液代谢组学差异。该研究建立了具有潜在诊断和预后意义的尿液代谢物生物标志物组,其功能分析显示了CSDH更深层次的代谢紊乱,这可能有助于改善CSDH的早期临床诊断。
{"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}
引用次数: 0
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. 含缬氨酸蛋白(VCP/p97)对儿童AML的预后不利,并与未折叠蛋白反应蛋白IRE1和GRP78呈负相关:儿童肿瘤组的一份报告。
IF 2.1 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-11-01 Epub Date: 2023-06-07 DOI: 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.

目的:内质网(ER)是细胞内蛋白质合成和折叠的主要部位。ER相关降解(ERAD)和未折叠蛋白反应(UPR)是ER介导的细胞应激适应的主要机制。靶向细胞应激反应是治疗急性髓系白血病(AML)的一种很有前途的方法。实验设计:使用反相蛋白质阵列方法,在483名儿童AML患者的外周血样本中测量了ERAD的主要成分缬氨酸蛋白(VCP)的蛋白质表达水平。患者参加了儿童肿瘤组AAML1031的3期临床试验,该试验将患者随机分为标准化疗(阿糖胞苷(Ara-C)、柔红霉素和依托泊苷[ADE])和ADE加硼替佐米(ADE+BTZ)。结果:与中高VCP表达相比,低VCP表达与良好的5年总生存率(OS)显著相关(81%对63%,p结论和临床相关性:我们的研究结果表明,蛋白VCP作为预测儿童AML预后的生物标志物具有潜力。
{"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}
引用次数: 0
Proteomics and bioinformatics investigations to improve serological diagnosis of canine brucellosis. 蛋白质组学和生物信息学研究提高犬布鲁氏菌病的血清学诊断。
IF 2 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-11-01 Epub Date: 2023-08-02 DOI: 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.

目的:犬布鲁氏菌对犬和人都具有致病性。血清学诊断是一种具有成本效益的疾病监测方法,但目前血清学检测的一个主要缺点是与其他细菌的交叉反应性,导致假阳性反应。开发具有提高灵敏度和特异性的间接检测方法,使用选定的犬B.蛋白而不是整个抗原,仍然是一个优先事项。实验设计:利用一组阳性和阴性狗血清,开发了一种免疫印迹法来确定与感染相关的血清抗体模式。犬B.阳性血清可识别7 - 30 kDa的免疫原性条带,然后将其提交ESI-LC-MS/MS并通过生物信息学工具进行分析。结果:共鉴定出398个犬双球菌蛋白。生物信息学工具鉴定出16种非细胞质免疫原性蛋白,预测与最重要的布鲁氏菌交叉反应菌非同源,9种犬双歧杆菌蛋白与羊双歧杆菌非同源;在后者中,一个结果与B. melitensis非同源。数据可通过ProteomeXchange获得,标识符为PXD042682。结论和临床意义:开发的western blotting试验能够区分感染和未感染的动物,并可作为犬B.的血清学诊断的确证试验。质谱分析和计算机分析结果可鉴定出特定的候选抗原,为开发更准确的间接诊断测试铺平道路。
{"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}
引用次数: 0
Realm of proteomics in breast cancer management and drug repurposing to alleviate intricacies of treatment. 蛋白质组学在乳腺癌管理和药物再利用领域,以减轻治疗的复杂性。
IF 2 4区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-11-01 Epub Date: 2023-05-31 DOI: 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.

乳腺癌是一种多网络异质性疾病,已成为临床肿瘤学发展的严重障碍。尽管技术进步和新兴的癌症研究已经降低了乳腺癌的致死率,但尚未实现精确的癌症导向解决方案。因此,这篇综述将说服人们默认基于蛋白质组学的乳腺癌诊断和治疗选择。最近,通过成像蛋白质组学、单细胞蛋白质组学、相互作用组学和翻译后修饰(PTM)跟踪来构建蛋白质组图和蛋白质分型以进行阶段特异性和样本特异性癌症分型的乳腺癌健康监测的证据,通过提高诊断效率、预后价值和预测反应,超过了传统的乳腺癌治疗方法。此外,还阐述了应用蛋白质组学设计化疗方案以确定具有轻微副作用的新药物靶点的范式转变。最后,讨论了蛋白质组学在减轻化疗耐药的发生和提高重组药物的有效性以对抗治疗障碍方面的潜力。由于蛋白质组学技术的巨大潜力,蛋白质组学在乳腺癌管理中的临床识别是可以实现的,治疗的复杂性可以克服。
{"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}
引用次数: 1
期刊
PROTEOMICS – Clinical Applications
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1