确定胃癌的蛋白质生物标记物:基于质谱的标记物目录,评估其在靶向蛋白质组学应用中的适用性。

IF 2.8 2区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS
Poornima Ramesh , Mahammad Nisar , Neha , Shruthi Ammankallu , Sreeranjini Babu , Revathy Nandakumar , Chandran S. Abhinand , Thottethodi Subrahmanya Keshava Prasad , Jalaluddin Akbar Kandel Codi , Rajesh Raju
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引用次数: 0

摘要

胃癌(GC)是全球关注的健康问题。为了改善对胃癌的管理,人们通过基于质谱的蛋白质组学平台确定了蛋白质生物标志物。为了展示这些数据的临床实用性,我们从蛋白质组学研究中收集了 6,800 多种胃癌中的差异调控蛋白质,并记录了质谱平台、蛋白质与感染性病原体的关联、蛋白质标识符、样本大小和所用样本的临床特征以及验证细节。开发有针对性的蛋白质组学方法是将这些标记物应用于临床的基石。因此,我们开发了胃癌蛋白质生物标记物矩阵(PBMGC),这是一个简单的每种蛋白质的稳健性目录。通过分析,我们确定了组织、血清、尿液和预后蛋白的稳健性,可进一步测试其临床实用性。我们还确定了适合开发 MRM 检测的 5631 种蛋白质的蛋白型胰蛋白酶肽。我们对这些肽进行了广泛的表征,以记录肽离子、质量/电荷和增强的特定肽特征。为了满足蛋白质组学研究人员的需求,这项分析产生的数据已编入胃癌蛋白质组学数据库(GCPDB)(https://ciods.in/gcpdb/)。用户可以浏览和下载数据,并通过提交最近发表的数据来完善 GCPDB。意义:基于质谱的蛋白质组学平台已积累了大量有关胃癌(GC)临床样本中蛋白质差异调控的数据。这些数据在临床应用中的效用受到了限制,因为需要寻找合适的生物标记物来评估胃癌。我们从蛋白质组学研究中收集了 6800 多种胃癌中的差异调控蛋白质,并记录了相应的详细信息,包括质谱平台、蛋白质与感染性病原体的关联情况、不同数据库中的蛋白质标识符、测试和对照条件下所用样本的样本大小和临床特征,以及验证的详细信息。为了在临床检测中利用这些标记物,我们开发了胃癌蛋白质生物标记物矩阵(PBMGC),并确定了与临床相关的多蛋白面板。我们还展示了 5631 种胃癌生物标志物蛋白质的胰蛋白酶肽型的鉴定和表征,这些胰蛋白酶肽型适合在 SCIEX QTRAP 仪器上开发多反应监测(MRM)测定。为了满足蛋白质组学研究人员的需求,该分析产生的数据已编入胃癌蛋白质组学数据库(GCPDB)(https://ciods.in/gcpdb/)。用户可以浏览和下载不同标记物的详细信息,并通过提交最近发表的数据来完善 GCPDB。这样的分析可以为建立更多此类资源或在不同临床条件下进行此类分析奠定基础,以吸收和发展靶向蛋白质组学作为临床应用的首选方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Delineating protein biomarkers for gastric cancers: A catalogue of mass spectrometry-based markers and assessment of their suitability for targeted proteomics applications

Delineating protein biomarkers for gastric cancers: A catalogue of mass spectrometry-based markers and assessment of their suitability for targeted proteomics applications

Gastric cancer (GC) is a global health concern. To facilitate improved management of GCs, protein biomarkers have been identified through mass spectrometry-based proteomics platforms. In order to exhibit clinical utility of such data, we congregated over 6800 differentially regulated proteins in GCs from proteomics studies and recorded the mass spectrometry platforms, association of the protein with infectious agents, protein identifiers, sample size and clinical characters of samples used with details on validation. Development of targeted proteomics methods is the cornerstone for pursuing these markers into clinical utility. Therefore, we developed Protein Biomarker Matrix for Gastric Cancer (PBMGC), a simple catalogue of robustness of each protein. This analysis yielded the identification of robust tissue, serum, and urine diagnostic and prognostic protein biomarker panels which can be further tested for their clinical utility. We also ascertained proteotypic tryptic peptides of 5631 proteins suitable for developing multiple reaction monitoring (MRM) assays. Extensive characterization of these peptides was carried out to record peptide ions, mass/charge and enhanced specific peptide features. With the vision of catering to proteomics researchers, the data generated through this analysis has been catalogued at Gastric Cancer Proteomics DataBase (GCPDB) (https://ciods.in/gcpdb/). Users can browse and download the data and improve GCPDB by submitting recently published data.

Significance

Mass spectrometry-based proteomics platforms have accumulated substantial data on proteins differentially regulated in gastric cancer (GC) clinical samples. The utility of such data in clinical applications is limited by search for suitable biomarker panels for assessment of GCs.

We assembled over 6800 differentially regulated proteins in GCs from proteomics studies and recorded the corresponding details including mass spectrometry platforms, status on the association of the protein with infectious agents, protein identifiers from different databases, sample size and clinical characters of samples used in test and control conditions along with details on their validation.

Towards the vision of utilizing these markers in clinical assays, Protein Biomarker Matrix for Gastric Cancer (PBMGC) was developed and clinically relevant multi-protein panels were identified. We also demonstrated identification and characterization of tryptic proteotypic tryptic peptides of 5631 proteins biomarkers of GCs which are suitable for development of MRM assays in a SCIEX QTRAP instrument.

Aimed to caterproteomics researchers, the data generated through this analysis has been catalogued at Gastric Cancer Proteomics DataBase (GCPDB) (https://ciods.in/gcpdb/). The users can browse and download details on different markers and improve GCPDB by submitting recently published data.

Such an analysis could lay a cornerstone for building more such resources or conduct such analysis in different clinical conditions to uptake and develop targeted proteomics as the method of choice for clinical applications.

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来源期刊
Journal of proteomics
Journal of proteomics 生物-生化研究方法
CiteScore
7.10
自引率
3.00%
发文量
227
审稿时长
73 days
期刊介绍: Journal of Proteomics is aimed at protein scientists and analytical chemists in the field of proteomics, biomarker discovery, protein analytics, plant proteomics, microbial and animal proteomics, human studies, tissue imaging by mass spectrometry, non-conventional and non-model organism proteomics, and protein bioinformatics. The journal welcomes papers in new and upcoming areas such as metabolomics, genomics, systems biology, toxicogenomics, pharmacoproteomics. Journal of Proteomics unifies both fundamental scientists and clinicians, and includes translational research. Suggestions for reviews, webinars and thematic issues are welcome.
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