Serum Protein Profiling of Patients at Risk to Develop Gastric Disease Based on a DSC Test

Background: At present, the gold standard for gastric cancer (GC) confirmation relies mostly on histopathology, an invasive procedure. Noninvasive detection methods using serum for large-scale screening maybe useful for the early diagnosis of GC. Helicobacter pylori (HP) infection and chronic atrophic gastritis are major GC risk factors. We recently developed a noninvasive test called DSC test—, based on patient’s age, sex, their serum PGI and PGII, anti-HP immunoglobulin (IgG), and gastrin G17 levels –predicting GC risk as low (score 0, S0) or high (score 2, S2). The comparative investigation at serum protein level of the two different patient groups detected by our DCS test (S0 and S2) may undoubtedly help to identify gastric disease-dependent proteins, resulting from bacterial infection or gastric mucosa inflammation, as well as get better insight the molecular scenario associated to pre-cancerous conditions. Methods: Mass spectrometry-based protein analysis of tryptically digested proteins was performed, followed by univariate statistical analysis for the different DSC groups from two cohort of patients (exploratory and validation). Significantly differentially abundant proteins differing more than 1.5-fold between groups were selected and validated, and their putative role(s) in gastritis and GC discussed. Results: We present data of comparative protein analysis of sera from patients at high risk to develop gastric cancer or advanced atrophy, depending on their DSC score. In particular, we used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics as semiquantitative method to profile proteins specifically associated with score 2 in sera of 80 patients. In both the exploratory and the validation cohorts, four proteins (beta-2-microglobulin, EGF-containing fibulin-like extracellular matrix protein 1, complement factor D, and Cystatin-C) were more abundant, while two (sex hormone-binding globulin and pregnancy zone protein) were less abundant in sera of S2 individuals (|fold change|≥0.6, p < 0.05, t-test). The higher presence of beta-2-microglobulin (B2M) and the lower content of pregnancy zone protein (PZP) in S2 sera were validated by immunoblotting. Conclusions: This study identified a proteomic signature differentially associated to sera of patients with a different risk to develop GC/advanced atrophy according to our DSC test. The protein marker panels presented in this work will contribute to improve GC diagnostics, once they have been transferred from a research result to a practical tool.