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- Title
Molecular features and prognostic factors of locally advanced microsatellite instability-high gastric cancer.
- Authors
Furukawa, Kenichiro; Hatakeyama, Keiichi; Terashima, Masanori; Urakami, Kenichi; Koseki, Yusuke; Fujiya, Keiichi; Tanizawa, Yutaka; Bando, Etsuro; Yamaguchi, Ken
- 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.
- Subjects
STOMACH cancer; PROGNOSIS; MICROSATELLITE repeats; GASTRECTOMY; GENE expression profiling; TUMOR classification
- Publication
Gastric Cancer, 2024, Vol 27, Issue 4, p760
- ISSN
1436-3291
- Publication type
Article
- DOI
10.1007/s10120-024-01506-5