TP53 somatic mutations are associated with poor survival in non-small cell lung cancer patients who undergo immunotherapy.

Aging
Liqin ZhaoWeiJian Guo

Abstract

In this study, we investigated the association between TP53 somatic mutations and immunotherapeutic outcomes in non-small cell lung cancer (NSCLC) patients. Kaplan-Meier survival curve analysis of the MSK-IMPACT cohort of 350 NSCLC patients shows that overall survival (OS) is significantly lower for patients with truncating TP53 mutations than those with wild-type TP53 (OS: 9 months vs. 14 months; P=0.019). Multivariate analysis shows that truncating TP53 mutations are an independent predictor of immunotherapeutic outcomes. Moreover, among NSCLC patients with lower tumor mutation burden (TMB), those with TP53 truncating mutations showed significantly lower OS than those with wild-type TP53 [hazard ratio (HR) = 1.40, confidence interval (CI) = 1.13-1.73; P = 0.002]. TP53 mutations correlate with higher infiltration of CD8+ T cells, neutrophils and dendritic cells in lung adenocarcinoma tissues. A prognostic model with TP53 mutational status shows better survival prediction than the model without TP53 mutational status 1-year [area under curve (AUC): 64.9% vs. 60.2%; P = 0.052] and 2-years (AUC: 70.9% vs. 66.1%; P = 0.098) post-immunotherapy. These findings demonstrate that truncating TP53 mutations correlate with poor immunother...Continue Reading

References

Jan 24, 2012·The European Respiratory Journal·Chiara ScocciantiUNKNOWN European Early Lung Cancer Consortium
Jan 17, 2014·The Lancet. Respiratory Medicine·Giulia M StellaPaolo M Comoglio
Jul 21, 2015·Nature Medicine·Andrew J GentlesAsh A Alizadeh
Aug 21, 2015·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·William D TravisUNKNOWN WHO Panel
Sep 24, 2015·Nature Reviews. Molecular Cell Biology·Søren Lykke-Andersen, Torben Heick Jensen
Sep 29, 2015·The New England Journal of Medicine·Hossein BorghaeiJulie R Brahmer
Jan 17, 2016·Nucleic Acids Research·Nele HugJavier F Cáceres
May 31, 2016·Nature Genetics·Bo LiX Shirley Liu
Nov 3, 2016·Cold Spring Harbor Perspectives in Medicine·Pierre Hainaut, Gerd P Pfeifer
Aug 31, 2016·Lancet·Fred R HirschLuis Paz-Ares
Jan 1, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Zhong-Yi DongYi-Long Wu
Sep 26, 2017·Translational Cancer Research·Mitchell W Braun, Tomoo Iwakuma
Dec 16, 2017·Nature Reviews. Cancer·Vladimir J N BykovKlas G Wiman
Feb 21, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D WestoverL Paz-Ares
May 17, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jérôme BitonDiane Damotte
Jan 16, 2019·Nature Genetics·Robert M SamsteinLuc G T Morris
Feb 21, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Neal ReadySuresh S Ramalingam
May 18, 2019·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Sandra AssounGérard Zalcman
Aug 21, 2019·Computational and Structural Biotechnology Journal·Haoyu LyuXiaosheng Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing

Software Mentioned

TIMER
R

Related Concepts

Related Feeds

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.