Abstract
Abstract
Background
This study aimed to reveal the effect of TP53 status on clinical outcomes and underlying mechanism in gastric cancer (GC) patients.
Methods
TP53 status was divided into three groups according to genome sequencing, namely clonal mutations with LOH (C-LOH), clonal diploid or subclonal mutations (CD-SC), and wild type (WT). The p53 protein activity was divided into over-expression (OE), Null and WT according to immunohistochemical staining. Four cohorts, including the TCGA, SMC, ZSHS and FUSCC cohort, were analyzed for association between TP53 mutation status and clinical outcomes and the underlying mechanism.
Results
In TCGA cohort, TP53 CD-SC were associated with superior overall survival compared to TP53 C-LOH cases. GC patients could benefit from ACT only in TP53 CD-SC/ p53 OE and TP53/ p53 WT subgroups, and TP53 C-LOH subgroup demonstrated the worst response to pembrolizumab among three subgroups. Genomic and immunophenotypic deconvolution revealed that TP53 C-LOH, CD-SC and WT differed for genomic and immune-related features.
Conclusions
TP53 C-LOH GCs with genomic instability and immune evasion phenotype have poor clinical outcomes in patients treated with ACT or immunotherapy.
Funder
National Natural Science Foundation of China
China Postdoctoral Science Foundation
Natural Science Foundation of Shanghai
Publisher
Springer Science and Business Media LLC