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Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer. | LitMetric

AI Article Synopsis

  • - The study investigates the relationship between tumour mutation burden (TMB) and the prognosis of patients with stage III gastric cancer, finding that high TMB correlates with better overall survival rates.
  • - Patients were categorized into high and low TMB groups using genetic sequencing and analysis, revealing that age is a key independent factor influencing prognosis, while TMB plays a significant, but secondary role.
  • - The research identifies that genes frequently mutated in gastric cancer are associated with certain signaling pathways, suggesting that TMB could serve as a useful biomarker for clinical outcomes in these patients.

Article Abstract

Introduction: To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC).

Methods: Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients and the Cancer Genome Atlas (TCGA) cohort of 173 patients. In the study cohort, next-generation sequencing was used to detect mutated GC genes and obtain TMB data. In the TCGA cohort, gene set enrichment analysis was performed, and the relationship between TMB, prognosis and clinicopathologic factors was analysed. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression levels of both proteins and genes. Cell viability was measured using methyl thiazolyl tetrazolium and transwell cell assays.

Results: Patients in the high TMB group had better overall survival (OS) rates than patients in the low TMB group for both cohorts and TMB was associated with age, mutation signature 1 and mutation signature 17. The Cox regression analysis revealed that age, not TMB, was an independent prognosis factor. Furthermore, genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch signalling pathways. The activation of these pathways was lower in the high TMB compared with the low TMB group, and the proliferation and migration abilities of GC cells showed a similar pattern in both TMB groups.

Conclusion: Patients in the high TMB group had better OS rates than patients in the low TMB group. Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530966PMC
http://dx.doi.org/10.34172/bi.2024.30118DOI Listing

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