Proteomic Helicobacter pylori biomarkers discriminative of low-grade gastric MALT lymphoma and duodenal ulcer

Abstract

To date no reliable diagnostic method exists to predict, among the very large and clinically heterogeneous group of Helicobacter pylori-infected patients, the extremely small group at risk for developing low-grade gastric MALT lymphoma (LG-MALT). Search of proteomic biomarkers holds promise for the classification of the H. pylori strains with regard to this severe clinical outcome. In the present study 69 H. pylori strains isolated from patients with two different H. pylori-associated diseases, duodenal ulcer (DU, n=29) and LG-MALT (n=40) were used. Protein expression patterns of the strains were analyzed by using the high-throughput methodology SELDI. Selected proteins were purified by means of chromatographic and electrophoretic methods in view of further sequencing by LC-MS/MS. Univariate analysis (Mann-Whitney test) of the protein expression patterns generated nine significant biomarkers that can discriminate between H. pylori strains from patients with DU and LG-MALT. These biomarkers are of low molecular weight, ranging from 6 to 26.6 kDa. Among them, two are overexpressed in LG-MALT strains and seven - in DU strains. Two biomarker proteins, one overexpressed in LG-MALT strains (13.2 kDa) and another one - overexpressed in DU strains (26.6 kDa), were purified to homogeneity and identified by using LC-MS/MS as a 50S ribosomal protein L7/L12 and a urease subunit, respectively. These biomarkers can be included in novel protein arrays for the differential diagnosis of H. pylori-associated clinical outcomes.