Jennifer Byrne , 2025-05-05 18:11:00
Key takeaways:
- Mutations in BRCA2, CDH1, RHOA and TP53 genes were associated with significantly worse disease-free survival and overall survival.
- These findings may help develop more targeted treatments.
SAN DIEGO — Researchers have identified four key genes — BRCA2, CDH1, RHOA and TP53 — whose mutations appear to be associated with development and progression of gastric cancer, according to a presenter at Digestive Disease Week.
Patients with pathologic variations in these genes had significantly worse disease-free and overall survival, findings showed.
“This is the first time we’re showing that these four genes are strongly related to outcome,” Ulysses Ribeiro, MD, PhD, professor of digestive system surgery at University of São Paulo School of Medicine and surgical coordinator of Cancer Institute of the State of São Paulo, said during his presentation. “It suggests that there’s more than one pathway through which stomach cancers form and that some are much more aggressive than others. That means patients without high-risk mutations could receive less aggressive treatment in some cases and be spared unnecessary side effects.”
Ribeiro and colleagues evaluated 21 genes in resected tumor samples from 87 patients treated with curative gastrectomy, lymphadenectomy and chemotherapy or immunotherapy for gastric cancer. They used Cox regression analysis to assess the prognostic value of genes with pathogenic variant (PV) and variant of uncertain significance (VUS).
“We used whole-genome sequencing to identify mutations that might affect how cancer behaves,” Ribeiro said
Researchers identified four genes — BRCA2, CDH1, RHOA and TP53 — with PV and VUS that affected prognosis.
Notably, a third of the patients (n = 29) had pathogenic or VUS mutations in these four genes. These patients had significantly worse disease-free survival (P = .005) and overall survival (P = .009) than those without mutations.
Multivariate analysis also showed that more advanced TNM pathological stage and identification of PV or VUS in the four genes were independently linked to worse disease-free survival.
“These patients were more likely to have their cancer come back or die from the disease, even after surgery and the best chemotherapy and immunotherapy,” he said. “These findings held up even after accounting for factors like cancer stage.”
Ribeiro said he and his team are working to utilize this information in commonly available lab tests that detect gene expression through immunohistochemistry. This could enable clinicians to more affordably and easily screen tumors for high-risk features.
“We are looking at how these mutations relate to protein markers that can be detected in whole-gene lab tests,” he said. “We can find these links between alterations in the immunocytokines, for example. It could make screening more accessible, especially in places where sequencing isn’t widely available.”
Ribeiro noted that although much of the previous research in gastric cancer has evaluated populations in East Asia, this study highlighted important genetic patterns in Western populations, particularly individuals of European and Latin descent in Brazil.
“This study finds a clear genetic signature that can help identify patients with especially poor outcomes in gastric cancer,” Ribeiro said. “This is a step toward more precise and more equitable treatment for gastric cancer and a foundation for further research in global populations.”
For more information:
Ulysses Ribeiro, MD, PhD, can be reached at gastroenterology@healio.com.
Sources/Disclosures
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Ribeiro U, et al. Next-generation DNA sequencing identifies somatic mutations associated to prognosis in gastric cancer patients. Presented at: Digestive Disease Week; May 3-6, 2025; San Diego.
Disclosures:
Healio could not confirm relevant financial disclosures at the time of publication.
