Abstract 149P
Background
Gastric cancer (GC) is one of the most common malignancies and a leading cause of cancer deaths worldwide. Currently, the genomic researches mainly focused on metastatic GC, but the clinico-molecular characteristics of resectable GC were poorly investigated.
Methods
A total of 47 resectable GC patients were enrolled. All kinds of genomic mutations were identified by next-generation sequencing (NGS) with Acornmed panel. Programmed death-ligand 1 (PD-L1) expression was analyzed by immunohistochemistry staining.
Results
Overall, a total of 582 mutations were identified from all the patients. TP53, LRP1B, ARID1A, and MDC1 were the most commonly mutated genes in resectable GC. Genomic data revealed significant mutual exclusivity between alterations in TP53 and PIK3CA (p < 0.05) and between those in TP53 and DICER1 (p < 0.05), as well as mutual co-occurence between alterations in FAT1 and ERBB3 (p < 0.05) and between those in FAT1 and NOTCH2 (p < 0.05). Additionally, ARID1A and APC alterations were significantly associated with poor differentiation (p < 0.05), and frequency of ARID1A mutations was markedly higher in intestinal-type GC than diffuse GC (p < 0.05). PD-L1 expression was analyzed in 45 tumors, and 33.3% of them showed positive PD-L1 expression. Further analysis demonstrated that KMT2D and ARID1A alterations were strikingly correlated with positive PD-L1 expression (p < 0.05). The median tumor mutational burden (TMB) in resectable GC was 6.38 mutations/Mb, and AR, CDH1, NOTCH2, and FAT1 mutations were remarkably associated with high TMB (p < 0.05). We further found that patients with positive PD-L1 expression tended to have low TMB (p = 0.057).
Conclusions
This study is of great significance in understanding the population characteristics of patients with resectable GC, which will be useful to guide personalized therapy and promote the clinical management in this population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Zhi Zheng.
Funding
Beijing Municipal Science & Technology Commission.
Disclosure
All authors have declared no conflicts of interest.
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