Molecular features and prognostic factors of locally advanced microsatellite instability-high gastric cancer.
Gastric Cancer
; 27(4): 760-771, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38744779
ABSTRACT
BACKGROUND:
Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer.METHODS:
This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer.RESULTS:
MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group.CONCLUSIONS:
The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
/
Inestabilidad de Microsatélites
/
Gastrectomía
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Gastric Cancer
Asunto de la revista:
GASTROENTEROLOGIA
/
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón