Abstract 1229P
Background
Genetic alterations in TP53 gene occurs between 5-80% of cancers. Numerous studies have reported the prognostic implications of certain TP53 mutations at specific sites, mutation types and functional effects. We aimed to explore the potential of TP53 mutations as prognostic markers in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).
Methods
We retrieved the genomic and clinical data from publicly-available pan lung cancer dataset from The Cancer Genome Atlas. The dataset was comprised of 1,053 patients, including 566 LUAD and 487 LUSC. We analyzed the disease-free (DFS) and overall (OS) survival outcomes of TP53-mutant and TP53 wild-type (WT) NSCLC.
Results
TP53 mutations were detected from 52% (264/566) of the LUAD and 86% (401/487) of the LUSC patients. Among the LUAD patients, TP53-mutants have significantly more co-occurring mutations than TP53-WT patients. Consistently, TP53-mutant LUAD patients have significantly higher tumor mutation burden (TMB) than TP53-WT patients (P<0.01). Significant mutual exclusive relationship was found between TP53 and KRAS mutations in TP53-mutant LUAD patients (P=0.002). Among the LUSC patients, TMB were similar between TP53-mutant and TP53-WT patients. However, among the TP53-mutant LUSC patients, those who harbored mutations in exons 5-8 had significantly higher TMB than those whose mutations are located in other regions (P=0.002). Survival analysis among TP53-mutant LUSC patients revealed a shorter DFS for those with LOF mutations than those with non-LOF mutations (P=0.04). Moreover, OS was significantly shorter for TP53-mutant LUAD patients than TP53-WT (41.6 vs. 53.3 mo; P=0.03); while OS was significantly longer for TP53-mutant LUSC patients than TP53-WT (61.6 vs. 29.0 mo; P=0.01).
Conclusions
Our study demonstrates a significantly higher TMB for TP53-mutant LUAD patients, suggesting a possibility of exploring TP53 mutations as additional markers for immunotherapy response. In addition, we also revealed a histology-specific difference in overall survival outcomes for TP53-mutants, suggesting distinct prognostic implications of TP53 mutations in various histology or even other tumor types. These promising results warrant further investigation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Cancer Research Program of National Cancer Center.
Disclosure
All authors have declared no conflicts of interest.