Gastric cancer remains one of the leading causes of cancer-related deaths worldwide, in part due to late-stage diagnosis and the complex web of genetic, environmental, and microbial risk factors. Although H. pylori infection is a known driver, its eradication alone cannot fully explain individual variability in cancer outcomes. In recent years, scientists have turned their attention to metabolic signatures—chemical fingerprints left behind by the body's cellular processes—as potential markers for disease risk. However, most metabolomics studies rely on observational data, limiting their power to prove cause and effect. Due to these challenges, there is a pressing need to identify causal biomarkers that can both signal cancer risk and inform personalized prevention strategies.
Researchers from Peking University Cancer Hospital & Institute published a study (DOI: 10.20892/j.issn.2095-3941.2024.0523)in Cancer Biology & Medicine that connects plasma L-aspartic acid levels to the development and prevention of gastric cancer. By integrating multi-stage metabolomic data, Mendelian randomization, and long-term intervention trial results, the team investigated how this metabolite not only predicts cancer risk but also alters the impact of preventive treatments. Their findings draw from data in both high-risk Chinese populations and European cohorts, providing strong evidence for L-aspartic acid as a dual-purpose biomarker for stomach cancer detection and intervention guidance.
The investigation began with a metabolomic case-control study in Linqu County, China—a region with high gastric cancer rates—where 14 metabolites were identified as linked to cancer risk. Among them, L-aspartic acid stood out. Using genetic instruments, researchers found that individuals with higher genetically predicted levels of this amino acid had a significantly increased risk of developing gastric cancer in two large Chinese cohorts, as well as an elevated risk of gastric adenocarcinoma in European populations.
But the story didn’t end there. The team went a step further by exploring how L-aspartic acid levels affected the success of established prevention strategies. In a 27-year randomized trial, the benefits of H. pylori eradication were seen only among individuals with high levels of L-aspartic acid, while garlic supplementation proved effective only in those with low levels. No such interaction was found with vitamin use. These findings suggest that L-aspartic acid not only signals cancer risk but also governs how the body responds to preventive measures—offering a promising route to targeted prevention. The integration of metabolomics and genetic tools allowed researchers to move beyond correlation to suggest causation, opening a new frontier in cancer risk prediction.
“Our findings suggest that plasma L-aspartic acid is not just a passive marker but an active player in gastric cancer development and prevention,” said Dr. Wenqing Li, senior author of the study. “This amino acid could help clinicians identify those at highest risk and determine which patients are most likely to benefit from specific interventions like H. pylori treatment or garlic supplementation. The era of “one-size-fits-all” prevention is coming to an end—we're now entering a phase of precision prevention driven by biology.”
The implications of this study are far-reaching. By incorporating plasma L-aspartic acid profiling into screening programs, health systems could more accurately identify high-risk individuals and allocate preventive resources more effectively, though further validation is warranted prior to clinical implementation. For example, those with elevated levels might be prioritized for H. pylori eradication therapy, while others could benefit more from dietary approaches. Beyond public health, these insights pave the way for targeted therapeutics focused on aspartate metabolism, a known factor in tumor cell proliferation. The study sets the stage for future research into metabolite-guided cancer prevention strategies—offering a personalized, biology-informed approach to reduce the burden of gastric cancer globally.
###
References
DOI
10.20892/j.issn.2095-3941.2024.0523
Original Source URL
https://doi.org/10.20892/j.issn.2095-3941.2024.0523
Funding Information
This study was funded by the National Natural Science Foundation of China (No. 82273704), Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2023ZD0501400-2023ZD0501402), Beijing Hospitals Authority’s Ascent Plan (DFL20241102), Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (No. ZLRK202325), China Postdoctoral Science Foundation (2024M760152), Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development (No. BMU2022XKQ004), and Science Foundation of Peking University Cancer Hospital (Nos. BJCH2024BJ02, XKFZ2410, BJCH2025CZ04, and 2022-27).
About Cancer Biology & Medicine
Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 8.4, 5-year IF 6.7), with all full texts freely visible to clinicians and researchers all over the world (http://www.ncbi.nlm.nih.gov/pmc/journals/2000/).