GEM research summary

Overview

The Gastric Hormone Biomarkers of Preneoplastic Lesions (GEM) study will investigate four potential new serologic biomarkers of stomach cancer precursor lesions. Research is taking place at the John Radcliffe Hospital in Oxford.

The study is registered at ClinicalTrials.gov: NCT06085677.

Background

Stomach cancer is the fifth most common cancer and fourth leading cause of cancer death worldwide, just one in five patients survive their disease beyond five years. Stomach cancer arises following chronic inflammation of the stomach, often resulting from infection with the bacteria, Helicobacter pylori (H. pylori). Persistent inflammation can result in destruction of the cells and glands lining the stomach (chronic atrophic gastritis). Following this destruction, the stomach epithelium can be replaced by intestinal-type epithelium (intestinal metaplasia) and for a small proportion of people this cascade of chronic inflammation can result in stomach cancer.

Stomach cancer has a long latency that contrasts strikingly with the small fraction of stomach cancer patients diagnosed at an early stage. The British Society of Gastroenterology recently concluded that “recognizing and targeting high risk patients…may be the most effective means to improve stomach cancer detection, and possibly survival, in the UK”. Early stomach lesions can be focal and may be missed on biopsy so alternative diagnostic methods are being sought. A serologic biomarker of stomach cancer precursor lesions could enable early detection and direct endoscopy to those who might benefit most.

We propose that the destruction of the gastrointestinal epithelium is mirrored in changes to the serologic levels of hormones and peptides secreted or metabolised by the gastrointestinal tract. To test whether these serum targets might be clinically useful, we need to understand whether they are associated with pre-cancerous lesions in a manner that could inform early detection and diagnosis.

Method

The study has recruited around 40 patients with normal epithelium or mild gastritis, chronic atrophic gastritis, or intestinal metaplasia.

These patients were invited to take part in the study when attending endoscopy procedures at the participating hospital in Oxford. Once consented, a blood sample was drawn, and a medical history questionnaire was completed.

National banked samples from patients who have previously consented to their sample being used in medical research will also be included.

The blood samples will be stored and tested for levels of ghrelin, total gastrin, vitamin B12, and pepsinogen 1 and 2. These levels will be correlated against stomach epithelium status.

Expected impact of results

In previous prospective studies, we have shown striking associations between gastrointestinal hormones/peptides and risk of upper gastrointestinal cancer in asymptomatic populations. We expect that measurements of these metabolites will be correlated with precursor lesion status, suggesting their potential use as biomarkers for stomach cancer.

We also expect that each metabolite could contribute specific information about the histologic health of the stomach, as our prior work has found little statistical correlation between ghrelin, vitamin B12, and gastrin, and no correlation with serum pepsinogens.

Future work will focus on leading larger clinical studies and the development of a multiplex assay for simpler testing of these metabolites in general labs.