Community Research and Development Information Service - CORDIS

Periodic Report Summary 1 - HELICOMARK (Antibody-responses to Helicobacter pylori and tumour proteins as biomarkers for early gastric cancer)

The project aim to identify antibody signatures to Helicobacter pylori infection and to tumour antigens as serological biomarkers for early gastric cancer. The work during the outgoing phase has been carried out in the laboratory of Professor Barry Marshall, University of Western Australia, Perth, and will in the return phase be done at the University of Gothenburg, Sweden.
To meet the over-all aim, the fellow focused efforts in two complementary areas: 1) to map H. pylori and host proteins of relevance during gastric cancer development, by analysing H. pylori gene expression in the stomach of individuals with precancerous conditions, and by studying host gene mutations in gastric cancer tissue; 2) to perform high-resolution mapping of the antibody-response to relevant H. pylori and tumour proteins using peptide arrays in order to identify antibody-response signatures that are discriminatory for early gastric cancer or for high gastric cancer risk.
Significant progress has been made during these first two years of the project. RNA-sequencing and RT-PCR analysis of stomach samples demonstrated that high expression of certain H. pylori genes is associated with gastric cancer risk. This was concluded since increased expression some H. pylori genes were found specifically in H. pylori-infected patients with precancerous lesions, while other H. pylori genes were expressed at a similar level in all H. pylori-infected individuals. The underlying hypothesis of the project is that high-resolution analysis of antibody-responses to such differentially expressed genes could be the basis for determining future gastric cancer risk in infected individuals, as well as for identifying individuals with early gastric cancer.
By high-resolution analysis of antibody-responses to H. pylori proteins the fellow identified several hundred linear B-cell epitopes within the H. pylori proteome. It was also shown that individuals with precancerous lesions showed a different diversity in their antibody-responses compared to individuals with uncomplicated gastritis. Furthermore, the B-cell epitopes of the immune-dominant virulence factor CagA was mapped in very high detail.
Based on the results from a large number of tested H. pylori peptides, a focused list of peptides will be tested in relevant patient cohorts during the final year of the project. These studies are believed to identify and confirm peptide collections that can be used to diagnose individuals with early gastric cancer or carrying a high-risk H. pylori infection. If this accomplished, the implications for health in relation to gastric cancer will be profound. It would then be possible to develop a low-cost minimally invasive screening test for gastric cancer, which would lead to early diagnosis and higher possibility of cure by current treatment regimens. Alternatively, a low-cost test for high-risk infection would increase the ability to identify and treat H. pylori infected individuals at high risk of gastric cancer development, and thereby reduce gastric cancer incidence.

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Life Sciences
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