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

Abstract

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.

Keywords: Biomarkers; Database; Mass spectrometry; Proteomics; Proteotypic peptides; Stomach neoplasms.