The characteristics and clinical relevance of tumor fusion burden in non-EBV (+) gastric cancer with MSS.
BMC Gastroenterol
; 23(1): 153, 2023 May 15.
Article
em En
| MEDLINE
| ID: mdl-37189078
ABSTRACT
BACKGROUND:
Next-generation sequencing (NGS) is maturely applied for gene fusion detection. Although tumor fusion burden (TFB) has been identified as an immune marker for cancer, the relationship between these fusions and the immunogenicity and molecular characteristics of gastric cancer (GC) patients remains unclear. GCs have different clinical significance depending on their subtypes, and thus, this study aimed to investigate the characteristics and clinical relevance of TFB in non-Epstein-Barr-virus-positive (EBV+) GC with microsatellite stability (MSS).METHODS:
A total of 319 GC patients from The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and a cohort of 45-case from ENA (PRJEB25780) were included. The cohort characteristics and distribution of TFB among the patients were analyzed. Additionally, the correlations of TFB with mutation characteristics, pathway differences, relative abundance of immune cells, and prognosis were examined in the TCGA-STAD cohort of MSS and non-EBV (+) patients.RESULTS:
We observed that in the MSS and non-EBV (+) cohort, the TFB-low group exhibited significantly lower gene mutation frequency, gene copy number, loss of heterozygosity score, and tumor mutation burden than in the TFB-high group. Additionally, the TFB-low group exhibited a higher abundance of immune cells. Furthermore, the immune gene signatures were significantly upregulated in the TFB-low group, 2-year disease-specific survival was markedly increased in the TFB-low group compared with to the TFB-high group. The rates of TFB-low cases were significantly higher TFB-than high cases in durable clinical benefit (DCB) and response groups with pembrolizumab treatment. Low TFB may serve as a predictor of GC prognosis, and the TFB-low group exhibits higher immunogenicity.CONCLUSION:
In conclusion, this study reveals that the TFB-based classification of GC patient may be instructive for individualized immunotherapy regimens.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Adenocarcinoma
/
Infecções por Vírus Epstein-Barr
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
BMC Gastroenterol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China