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Antibody-responses to Helicobacter pylori and tumour proteins as biomarkers for early gastric cancer

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

The project aimed 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 was carried out in the laboratory of Professor Barry Marshall, University of Western Australia, Perth, and during the return phase 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 was made during the outgoing phase 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 of 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.

During the return phase of the project, carried out at University of Gothenburg, H. pylori peptides were tested for antibody-responses in relevant patient cohorts. These studies identified peptides that can be used to diagnose individuals carrying an H. pylori infection associated with high gastric cancer risk. The implications of these results for health in relation to gastric cancer can be profound. Based on these findings, it may be possible to develop a low-cost minimally invasive screening test for high-risk infection. Such a test would increase the ability to identify H. pylori infected individuals at high risk of future gastric cancer development, and by eradicating their infection reduce gastric cancer incidence.

The results obtained from the return phase of the project has been filed in a patent application, and is being commercialised by the fellow within a startup company - Biotome. See www.biotome.se or contact samuel.lundin@biotome.se for more information.