Clinical and Prognostic Implications of an Immune-Related Risk Model Based on TP53 Status in Lung Adenocarcinoma

Abstract Background: TP53 mutation is the most widespread mutation in lung adenocarcinoma (LUAD), meanwhile p53 (encoded by TP53) has recently been implicated in immune responses. However, it is still unknown whether TP53 mutation may remodel tumor microenvironment to influence tumor progression and prognosis in LUAD.Methods: we developed a six-gene immune-related model (IRM) to predict the survival of patients with LUAD in TCGA cohort based on TP53 status using LASSO Cox analysis, which was also confirmed the predictive ability in two independent cohorts.Results: The mutation of TP53 led to a decrease in the immune response in LUAD. Further analysis revealed that patients in the high-index group had observably lower relative infiltration of memory B cells and regulatory T cells, together with significantly higher relative infiltration proportions neutrophils and resting memory CD4+ T cells. Additionally, the IRM index positively correlated with expression of critical immune checkpoint genes including PDCD1 (encoding PD-1) and CD274 (encoding PD-L1), which was validated in Nanjing cohort. Furthermore, the IRM index as an independent prognostic factor was used to establish a nomogram for clinical application.Conclusion: This immune-related model may serve as a powerful prognostic tool to further optimize immunotherapies for LUAD.