25 Apr DDW25: Genetic Signature of Gastric Cancer Can Help Identify Patients with Poor Outcomes

Dr. Ribeiro

MedicalResearch.com Interview with:
Ulysses Ribeiro M.D., PhD
Associate Professor of Digestive Surgery
Instituto do Câncer do Estado de São Paulo

MedicalResearch.com: What is the background for this study?

Response: Gastric cancer (GC) is one of the most common malignancies worldwide, and the 3th leading cause of cancer-related death. Although the diagnosis and treatment have substantially improved in recent years, the five-year survival rate of gastric cancer is still low due to local recurrence and distant metastasis.

Gastric cancer is a complex and heterogeneous disease that involves a series of genetic, epigenetic and phenotypic changes. Still, differences in prognosis and response to chemotherapy or immunotherapy are frequently seen in tumors with the same histological type and stage due to various genetic mutations and abnormal signaling pathways underlying the progression of this disease.

Thus, the purpose of this study was to perform a whole-gene sequencing to identify variants in genes with prognostic value in patients with gastric cancer who underwent curative surgery.

MedicalResearch.com: What are the main findings?

Response:  We analyzed tumor samples from 87 gastric cancer patients treated at São Paulo State Cancer Institute in São Paulo, Brazil. All patients had received standard treatment — surgery followed by chemotherapy — and we followed their outcomes over time.

We used whole-genome sequencing — a powerful technology that can quickly scan large amounts of DNA to identify mutations that might affect how a cancer behaves.

In this case, we looked at 21 genes and focused on those with either known harmful mutations or variants of uncertain significance (VUS)— changes we don’t fully understand yet but that could prove important.

We identified four genes — BRCA2, CDH1, RHOA, and TP53 — that were linked to significantly worse outcomes.

MedicalResearch.com: What should readers take away from your report?

Response: Our results are similar to some findings in the literature, such as regarding genes with the highest frequency of pathogenic mutations, such as TP53 and CDH1. However, as a differential, we also found a relationship between other genes and survival, including VUS in addition to alterations already described as pathogenic variants.

In other words, in our cohort of cases, it seems that some of these VUS may also have a negative impact on survival. This obviously should be evaluated later with a genomic database. Furthermore, as a differential, it is important to highlight that our study provide results from a Western cohort of patients who underwent curative treatment at a reference center, especially since most studies have been conducted in Eastern countries.

In summary, these findings reveal a clear genetic signature that can help identify patients with especially poor outcomes. This is a step toward more precise, more equitable treatment for gastric cancer — and a foundation for further research in global populations.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: In current practice, the results of our study do not yet directly imply changes in medical approach. First, the whole-genome research methods are difficult to implement in clinical practice due to their high cost and technical complexity. To overcome this barrier, it is necessary to provide a smaller set of the most informative diagnostic and prognostic markers for clinical application or even developed a prognostic modeling tool for GC based on gene signatures related to immuno-protein expression and specific pathological and morphological characteristics. In our study, for example, as a next step we are correlating the genetic alterations found with immuno-protein expression, in order to verify whether a pathogenic mutation or even a VUS reflects alterations in protein expression so that we can indirectly evaluate it by immunohistochemistry as a screening test, something feasible to apply in routine diagnosis.

Furthermore, validation of molecular results in large groups of patients with different ethnic and racial backgrounds is clearly needed before any changes in current screening and/or treatment practices.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Response: We characterized the mutational landscape of GC patients and discovered some new potential predictive markers of survival in curatively resected patients. At this point, it is clear that there cannot be a universal classification for GC, and molecular and genetic characteristics must be considered beyond the TNM staging to individualize and personalize both the prognosis and treatment of patients.

This study was supported by the State of Sao Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo- FAPESP) – Grant number: 2020/10878-7.

More information:

• American Cancer Society. (2025). Stomach Cancer. Retrieved April 24, 2025, from https://www.cancer.org/cancer/stomach-cancer.html

Citation:

Next-generation DNA sequencing identifies somatic mutations associated to prognosis in gastric cancer patients,” abstract 152, DDW2025   Digestive Disease Week April 2025

—–

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition.

Some links may be sponsored. Products are not warranted or endorsed.

Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

Last Updated on April 25, 2025 by Marie Benz MD FAAD