The characteristics and clinical relevance of tumor fusion burden in non-EBV (+) gastric cancer with MSS

Zhu，Yongjun1; Wu，Weixin2; Qiao，Liangliang3; Ji，Jingfen4; Duan，Lunxi4; Gong，Longlong5; Ren，Dandan5; Li，Feifei5; Wei，Lihui5; Pan，Ke4

2023-12-01

10.1186/s12876-023-02765-9

BMC Gastroenterology   影响因子和分区

1471-230X

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.

Gastric cancer Immunogenicity Prognosis Tumor fusion burden

SCI

英语

第一

Gastroenterology & Hepatology

Gastroenterology & Hepatology

WOS:000988976600004

BMC

CLINICAL MEDICINE

2-s2.0-85159271232

Scopus

1.Department of Gastrointestinal surgery,The Second Clinical Medical College,The First Affiliated Hospital,Shenzhen People’s Hospital,Jinan University,Southern University of Science and Technology),Shenzhen,518020,China
2.Department of Oncology,Zhongshan Hospital affiliated to Xiamen University,Xiamen,361004,China
3.Oncology Department I,Jinshazhou Hospital of Guangzhou University of Chinese Medicine,Guangzhou,510000,China
4.Department of General Surgery,The Second Xiangya Hospital of Central South University,Changsha,410011,China
5.Department of Medicine,Genecast Biotechnology Co.,Ltd,Wuxi,214000,China

Zhu，Yongjun,Wu，Weixin,Qiao，Liangliang,et al. The characteristics and clinical relevance of tumor fusion burden in non-EBV (+) gastric cancer with MSS[J]. BMC Gastroenterology,2023,23(1).

Zhu，Yongjun.,Wu，Weixin.,Qiao，Liangliang.,Ji，Jingfen.,Duan，Lunxi.,...&Pan，Ke.(2023).The characteristics and clinical relevance of tumor fusion burden in non-EBV (+) gastric cancer with MSS.BMC Gastroenterology,23(1).

Zhu，Yongjun,et al."The characteristics and clinical relevance of tumor fusion burden in non-EBV (+) gastric cancer with MSS".BMC Gastroenterology 23.1(2023).