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.

Proteomic Biomarkers Associated with Streptococcus agalactiae Invasive Genogroups

“…Each gel slice was further divided into two equal parts each corresponding to one lane. The target protein was extracted from one of these slices by passive elution as described previously [25], and the mass of the passively eluted target protein was confirmed on gold arrays. The proteins in the corresponding second slice were subjected to trypsin digestion and LC-MS/MS microsequencing as described below.…”

Diagnosis of Helicobacter pylori Infection

“…used another approach: surface‐enhanced laser desorption/ionisation time of flight (SELDI‐TOF) mass spectrometry to detect proteins specific for strains involved in specific diseases. They found an overexpression of a 50S ribosomal protein L7/L12 (13.2 kDa) in gastric MALT lymphoma and of a urease subunit (23.6 kDa) in peptic ulcer disease [37].…”

Complexomics Study of Two Helicobacter pylori Strains of Two Pathological Origins

“…RpL7/L12 was found both in the cytoplasm and membrane fractions (120,130). A recent study showed that RpL7/L12 is overexpressed in LG-MALT-associated strains when compared with DU-associated strains, suggesting that RpL7/L12 could be used as a biomarker for the differential diagnosis of H. pylori-associated clinical outcomes (17). RpL7/L12 was also reported previously to be overexpressed in gastric adenocarcinoma-associated strains (131).…”

“…Several studies examined the proteome of strains associated with different pathologies (47,48,79,80,128,131,143,(152)(153)(154)(155), most of them based on immunoproteomics methods. However, only one of these studies included strains associated with LG-MALT (17).…”

“…Thus, the RpL7/L12-NapA complex would be potentially implicated in the occurrence of gastric cancer. However, it was not possible to determine whether this complex is really specific to the B38 strain associated with LG-MALT because this complex could not be detected in the J99 strain where the RpL7/L12 protein is known to be expressed in smaller quantities (17). Moreover, it was recently demonstrated that NapA is able to prolong the lifespan of monocytes and neutrophils (134), which would contribute to the development of a malignant disease like LG-MALT.…”