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Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy
Liudmila V Spirina1,2, Alexandra V Avgustinovich2, Olga V Bakina2,3
1Biochemistry and Molecular Biology Division, Siberian State Medical University, 2 Moskovsky Trakt, Tomsk 634050, Russia.
Abstract:
Heterogeneity of gastric cancer (GC) is the main trigger of the disease's relapse. The aim of this study was to investigate the connections between targeted genes, cancer clinical features, and the effectiveness of FLOT chemotherapy. Twenty-one patients with gastric cancers (GCs) were included in this study. Tumor-targeted sequencing was conducted, and real-time PCR was used to assess the expression of molecular markers in tumors. Seven patients with stabilization had mutations that were related to their response to therapy and were relevant to the tumor phenotype. Two patients had two mutations. The number of patients with TP53 mutations increased in HER2-positive tumor status. PD-L1-positive cancers had mutations in KRAS, TP53, PIK3CA, PTEN, and ERBB, which resulted in an increase in PD-1 expression. TP53 mutation and PTEN mutation are associated with changes in factors associated with neoangiogenesis. In concusion, patients who did not have aggressive growth markers that were verified by molecular features had the best response to treatment, including complete morphologic regression.
Insights
Gastric cancer (GC) relapse is linked to tumor heterogeneity. Molecular markers and mutations, like TP53 and KRAS, influence FLOT chemotherapy effectiveness and patient response, impacting treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) heterogeneity drives disease relapse.
- Understanding molecular drivers is crucial for effective treatment strategies.
Purpose of the Study:
- Investigate links between targeted genes, clinical features, and FLOT chemotherapy efficacy in GC.
- Identify molecular markers associated with treatment response and tumor phenotype.
Main Methods:
- Tumor-targeted sequencing in 21 GC patients.
- Real-time PCR for molecular marker expression analysis.
Main Results:
- Seven patients with stabilization showed mutations linked to therapy response and tumor phenotype.
- TP53 mutations correlated with HER2-positive status.
- PD-L1-positive cancers exhibited mutations (KRAS, TP53, PIK3CA, PTEN, ERBB) increasing PD-1 expression.
- TP53 and PTEN mutations linked to neoangiogenesis factors.
Conclusions:
- Patients lacking aggressive molecular markers responded best to FLOT chemotherapy.
- Molecular profiling aids in predicting treatment effectiveness and patient outcomes in GC.
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