New study! Even if Helicobacter pylori is eradicated, the risk of gastric cancer still exists!

Gastric cancer, as one of the malignant tumors with a higher incidence rate worldwide, has always been a hot topic in medical research for its pathogenesis. In recent years, more and more studies have shown that Helicobacter pylori infection is closely related to the occurrence of gastric cancer. However, the scientific community has not yet fully clarified how Helicobacter pylori induces gastric cancer and why gastric cancer may still occur even after eradication. To this end, a research team led by Yang Shiming and Xiao Yufeng from the Second Affiliated Hospital of the Army Medical University (Xinqiao Hospital) is committed to in-depth exploration of the mechanism of Helicobacter pylori-induced gastric cancer, especially the "hit-and-run" hypothesis. The hypothesis holds that after Helicobacter pylori infection, even if it is later eradicated, certain damage to host cells or certain changes caused during the infection may persist, thereby continuing to promote the development of gastric cancer.

Research process and findings

The research team first focused on N6-methyladenosine (m6A), an important epigenetic modification of mRNA that can regulate processes such as mRNA stability, translation, and splicing, and is closely related to the occurrence and development of cancer. Through the analysis of gastric cancer tissue samples, the researchers found that the m6A level of mRNA was significantly reduced in gastric cancer samples positive for the virulence factor CagA (one of the main carcinogenic factors in Helicobacter pylori). At the same time, Helicobacter pylori infection experiments also showed that m6A levels were also reduced in cells infected with Helicobacter pylori that produced CagA.

Further studies have found that in CagA-positive gastric cancer, the expression level of FTO (an enzyme that can remove specific modified m6A in mRNA) is very high, and this high expression is associated with poor prognosis in patients. The specific mechanism is that CagA activates the ERK signaling pathway (an important signal transduction pathway in cells, involved in regulating various biological processes such as cell growth, differentiation, survival, and apoptosis), which in turn promotes the expression of FTO. After FTO removes the m6A modification on mRNA, it leads to increased expression of certain genes, and the increase of these genes promotes the migration and invasion ability of gastric cancer cells. Therefore, FTO plays a role in promoting tumor progression in CagA-positive gastric cancer.

To verify this mechanism, the research team conducted a number of experiments, including cell experiments, human database analysis, and mouse model experiments. They found that the expression level of FTO was significantly higher in CagA-positive gastric cancer tissues, and there was a correlation between the mRNA level of FTO and major clinical pathological characteristics such as lymph node metastasis, distant metastasis, and tumor stage. In addition, the study found that patients with high expression of FTO had a lower survival rate, suggesting that FTO may be a potential target for gastric cancer treatment.

The study also found that even eradication of Helicobacter pylori could not reverse the increased levels of FTO and HBEGF, suggesting that epigenetic changes induced by Helicobacter pylori infection are persistent and that their carcinogenic effects may persist even after Helicobacter pylori is eliminated.

After clarifying the above mechanism of action, the research team further explored potential treatment strategies. They combined meclofenamic acid, a non-steroidal anti-inflammatory drug and FTO inhibitor approved by the US FDA, with antibiotics. The results showed that the m6A level was increased, the expression of HBEGF (related to tumor progression, invasion and metastasis, high expression of HBEGF may promote the growth and spread of cancer cells) was inhibited, and the migration and invasion ability of gastric cancer cells was also weakened. This shows that the combination of meclofenamic acid and antibiotics can fight CagA-positive gastric cancer and provide patients with a new treatment option.

Future Outlook

This study by the Yang Shiming/Xiao Yufeng team provides a new perspective for understanding the relationship between Helicobacter pylori and gastric cancer, and also provides new ideas for the prevention and treatment of gastric cancer. In addition, given the prevalence of Helicobacter pylori infection, optimizing prevention strategies, such as early screening and eradication treatment, is also of practical significance for reducing the incidence of gastric cancer.

As we gain a deeper understanding of the relationship between Helicobacter pylori and gastric cancer, we are expected to develop more effective methods to prevent and treat this deadly disease in the future. The research conducted by the Yang Shiming/Xiao Yufeng team is undoubtedly an important step towards this goal. In the future, we expect more research to further reveal the carcinogenic mechanism of Helicobacter pylori and provide a more solid scientific basis for the prevention and treatment of gastric cancer.

References:

HeB, Hu Y, Wu Y, et al. Helicobacter pylori CagA elevates FTO to induce gastric cancerprogression via a “hit-and-run” paradigm. Cancer Communications (2025). doi:10.1002/cac2.70004