本研究旨在揭示TP53状态对胃癌（GC）患者临床结果的影响和潜在机制。TP53状态根据基因组测序分为三组，即带有LOH的克隆突变（C-LOH）、克隆二倍体或亚克隆突变（CD-SC）和野生型（WT）。根据免疫组化染色将p53蛋白活性分为过表达(OE)、Null和WT。包括 TCGA、SMC、ZSHS 和 FUSCC 队列在内的四个队列分析了 TP53 突变状态与临床结果和潜在机制之间的关联。在 TCGA 队列中，与 TP53 C-LOH 相比，TP53 CD-SC 与更高的总生存率相关案例。 GC 患者仅在 TP53 CD-SC/p53 OE 和 TP53/p53 WT 亚组中才能从 ACT 中受益，而 TP53 C-LOH 亚组在三个亚组中对派姆单抗的反应最差。基因组和免疫表型解卷积显示，TP53 C-LOH、CD-SC 和 WT 在基因组和免疫相关特征方面存在差异。具有基因组不稳定和免疫逃避表型的 TP53 C-LOH GC 在接受 ACT 或免疫治疗的患者中临床结果较差。© 2024。作者。

This study aimed to reveal the effect of TP53 status on clinical outcomes and underlying mechanism in gastric cancer (GC) patients.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.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.TP53 C-LOH GCs with genomic instability and immune evasion phenotype have poor clinical outcomes in patients treated with ACT or immunotherapy.© 2024. The Author(s).