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Volume 25, Issue 5
  • ISSN: 1389-2029
  • E-ISSN: 1875-5488

Abstract

Objective

This study aimed to investigate the frequently mutated genes in Gastric Cancer (GC), assess their association with Tumor Mutation Burden (TMB) and the patients’ survival, and identify the potential biomarkers for tailored therapy.

Methods

Simple somatic mutation data of GC were collected from the TCGA and ICGC databases. The high-frequency mutated genes were identified from both datasets. The samples were initially dichotomized into wild-type and mutation groups based on the status of overlapping genes. TMB difference between the two groups was evaluated by the Mann-Whitney U-test. Survival difference between the two groups was compared by the Kaplan-Meier method with a log-rank test. The prognostic value of the target gene was assessed by the Cox proportional hazards model. The signaling pathways involved in FAT4 mutation were identified by Gene Set Enrichment Analysis (GSEA). The fractions of different tumor-infiltrating immune cells were calculated by the CIBERSORT algorithm.

Results

21 overlapping genes with frequent mutation were identified in both datasets. Mutation of these genes was significantly associated with higher TMB (<0.05) in GC. The survival of the FAT4 mutation group was superior to the wild-type group. FAT4 mutation was also identified as an independent favorable prognostic factor for the GC patients. GSEA indicated that FAT4 mutation activated the signaling pathways involved in energy metabolism. Finally, CD4 memory-activated T cells, follicular helper T cells, and gamma delta T cells were significantly more enriched, while naïve B cells and regulatory T cells (Tregs) were significantly less enriched in the FAT4 mutation group (<0.05).

Conclusion

FAT4 mutation is relevant to TMB and favorable prognosis in GC, which may become a useful biomarker for immunotherapy of GC patients.

© 2024 Bentham Science Publishers
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2024-10-01
2024-11-22

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/content/journals/cg/10.2174/0113892029300694240612081006
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FAT4 Mutation is Related to Tumor Mutation Burden and Favorable Prognosis in Gastric Cancer
Curr. Genomics 25, 380 (2024); https://doi.org/10.2174/0113892029300694240612081006
/content/journals/cg/10.2174/0113892029300694240612081006
/content/journals/cg/10.2174/0113892029300694240612081006
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  • Article Type:     Research Article
Keyword(s): FAT4; Gastric cancer; prognosis; somatic mutation data of GC; tailored therapy; tumor mutation burden

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