ITRAQ and PRM-based quantitative saliva proteomics in gastric cancer: biomarker discovery

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Paper In "Frontiers in Molecular Biosciences"

Abstract

Background: Gastric cancer (GC) is a major global health issue with high mortality rates, primarily because over 80% of patients are diagnosed at an advanced stage. Current diagnostic methods, such as endoscopy, are invasive, while conventional tumor markers lack sensitivity for early detection. Salivary proteomics presents a promising, non-invasive, and cost-effective strategy for biomarker discovery.¹ This study aimed to identify differentially expressed salivary proteins (DEPs) in GC patients and evaluate their potential as novel non-invasive biomarkers.²

Methods: Salivary proteomes from two groups of GC patients (group 1: n = 12; group 2: n = 13) and healthy controls (n = 11) were analyzed using isobaric tags for relative and absolute quantitation (iTRAQ). DEPs were identified and subjected to functional annotation (GO, KEGG) and protein-protein interaction (PPI) network analysis. Candidate biomarkers were subsequently validated using parallel reaction monitoring (PRM).³

Results: A total of 671 proteins were identified. We found 124 and 102 significant DEPs in GC groups 1 and 2, respectively, compared to controls. Fifty-six overlapping DEPs were detected between the two GC cohorts, comprising 24 upregulated and 32 downregulated proteins. Functional analysis and PRM validation highlighted four key proteins with consistent differential expression: S100A8, S100A9, CST4, and CST5.⁴ Interestingly, while CST4 and CST5 were downregulated in the saliva of GC patients, they are reportedly upregulated in GC tissue and blood.⁵

Conclusion: Our findings demonstrate that specific salivary proteins, particularly S100A8, S100A9, CST4, and CST5, hold significant potential as a panel of non-invasive biomarkers for gastric cancer detection. These results provide new insights into saliva-based diagnostics and underscore the importance of cross-comparing biomarker expression across different biofluids and tissues.