Research Maps Molecular Links Between Stomach Infection and Cancer Risk

A recent study has uncovered significant molecular connections between Helicobacter pylori infection and the progression to gastric cancer, which is responsible for a substantial number of cancer-related deaths globally. The research, conducted by a team from the Peking University Cancer Hospital & Institute and other institutions, highlights the intricate biological processes that lead to the disease, providing new avenues for early detection and prevention strategies.

Gastric cancer typically develops through a series of changes: starting from superficial gastritis, advancing to chronic atrophic gastritis and intestinal metaplasia, and eventually leading to malignancy. Helicobacter pylori infection is implicated in nearly 90% of non-cardia gastric cancers, but the molecular mechanisms that facilitate this progression remain elusive. Traditional studies have often concentrated on isolated pathways, such as inflammation or immune response, lacking a broader integrative approach.

To address this gap, the research team applied advanced techniques, including large-scale proteomic profiling and single-cell transcriptomic sequencing, on gastric tissue samples from 166 individuals in Linqu, a high-risk region in China, and 99 patients in Beijing. Their findings were published in the journal Cancer Biology & Medicine in September 2025.

The study revealed over 4,200 proteins, from which 28 were validated as crucial markers of H. pylori infection and gastric cancer. Among these, proteins such as OLFM4 and ENO1 showed increased expression, while GSN and IGFBP2 were down-regulated. This data suggests a clear molecular signature linked to the progression of gastric lesions and cancer risk.

A significant aspect of the study was the analysis of protein expression variations as the disease progresses. Single-cell RNA sequencing of approximately 135,000 gastric cells demonstrated that these protein-encoding genes underwent stage-specific changes as cells transitioned from normal to precancerous states.

To assess the predictive capacity of these findings, the researchers developed a 15-protein tissue panel that effectively stratified patients by their risk of developing neoplasia. Notably, those in the highest risk quartile exhibited over a seven-fold increase in the odds of disease progression. The research further extended its implications by validating a four-protein circulating panel (including OLFM4, ENO1, GSN, and IGFBP2) within the UK Biobank cohort of 48,529 participants. Individuals identified as high-risk were reported to be nearly four times more likely to develop gastric cancer compared to those in the lowest risk category.

Dr. Wenqing Li, the senior author of the study, emphasized the importance of these findings: “By integrating tissue proteomics, single-cell sequencing, and long-term follow-up data, we have been able to identify consistent protein markers that map the stepwise development of gastric cancer.” This research not only enhances the understanding of how H. pylori infection alters the gastric environment but also provides vital tools for risk stratification.

The establishment of tissue-based and blood-based protein panels presents a transformative opportunity for gastric cancer prevention. Current endoscopic screening methods are often costly and invasive, limiting their applicability, particularly in resource-limited regions. The identification of non-invasive blood-based markers could facilitate large-scale population screening, targeting individuals who require urgent follow-up.

Beyond their clinical applications, the molecular signatures discovered in this study contribute to the broader understanding of infection-induced cancer biology. As these biomarkers undergo further validation, they could pave the way for precision medicine initiatives aimed at intercepting gastric cancer at its earliest stages.

This research was supported by several grants from the National Natural Science Foundation of China, among others, reflecting the collaborative effort to tackle this significant public health challenge.