A study in Gut shows that gastric cancer is shaped by complex interactions between environmental exposure, microbes, host, and tumor biology. The findings reveal distinct cancer routes and targets linked to prognosis and potential treatment opportunities.
A multidisciplinary collaborative research team from Taiwan, including National Taiwan University, Academia Sinica, and Kaohsiung Medical University Hospital, has published a comprehensive multi-omics study revealing how environmental exposure, microbial ecosystems, and host molecular responses jointly shape the development of gastric cancer.
The findings provide new insights into why gastric cancers arise through different biological routes and how these differences may influence patient outcomes.
Gastric cancer remains one of the leading causes of cancer mortality worldwide, particularly in East Asia. While Helicobacter pylori infection has long been recognized as a major driver of gastric carcinogenesis, the broader interactions among environmental exposures, microbial communities, and tumor biology have remained poorly understood.
To address this gap, the research team established a multi-omics atlas of gastric cancer by analyzing paired tumor and adjacent gastric mucosa tissues and blood from 154 treatment-naive patients in Taiwan.
The investigators integrated whole-exome sequencing, transcriptomics, proteomics, phosphoproteomics, microbiome profiling, and environmental carcinogen signatures to map the molecular landscape of the disease.
The study identified distinct carcinogenic exposure patterns linked to specific biological behaviors. In particular, a polycyclic aromatic hydrocarbon–related signature associated with dibenz[a,h]acridine was found to be strongly associated with tumor invasion, immune suppression, and poorer survival outcomes.
In addition, the analysis revealed three distinct ecological pathways of tumor initiation, including H. pylori-driven inflammatory tumors and two H. pylori-negative subtypes characterized by different microenvironments.
Among H. pylori-negative cancers, the researchers identified a Streptococcus-enriched subtype associated with disruption of epithelial tight junction proteins and activation of epithelial–mesenchymal transition pathways, suggesting a potential microbial influence on tumor progression.
Importantly, the team showed that utilizing environmental exposure signatures and tumor proteomic and immune features improved prediction of recurrence and survival beyond conventional clinical staging.
"For decades, gastric cancer development has often been described through the Helicobacter pylori–associated Correa cascade," said Professor Ming-Shiang Wu, Dean of the College of Medicine at National Taiwan University and co-corresponding author of this study.
"Our study shows that the disease can arise through multiple biological routes, reflecting the complex interplay of environmental exposure, microbial ecosystems and host responses."
Professor Sung-Liang Yu, Chair of the Department of Clinical Laboratory Sciences and Medical Biotechnology at National Taiwan University and co-corresponding author of the study, added, "The integration of multi-omics data provides a powerful tool for identifying biomarkers, improving molecular classification and developing new therapeutic strategies for gastric cancer."
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