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Clinical and prognostic implications of an immune‐related risk model based on TP53 status in lung adenocarcinoma

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 remodels the tumour microenvironment to influence tumour progression and prognosis in LUA...

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Autores principales: Song, Xuming, Chen, Qiang, Wang, Jifan, Mao, Qixing, Xia, Wenjie, Xu, Lin, Jiang, Feng, Dong, Gaochao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743672/
https://www.ncbi.nlm.nih.gov/pubmed/34877770
http://dx.doi.org/10.1111/jcmm.17097
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author Song, Xuming
Chen, Qiang
Wang, Jifan
Mao, Qixing
Xia, Wenjie
Xu, Lin
Jiang, Feng
Dong, Gaochao
author_facet Song, Xuming
Chen, Qiang
Wang, Jifan
Mao, Qixing
Xia, Wenjie
Xu, Lin
Jiang, Feng
Dong, Gaochao
author_sort Song, Xuming
collection PubMed
description 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 remodels the tumour microenvironment to influence tumour progression and prognosis in LUAD. In this study, we developed a 6‐gene immune‐related risk model (IRM) to predict the survival of patients with LUAD in The Cancer Genome Atlas (TCGA) cohort based on TP53 status, and the predictive ability was confirmed in 2 independent cohorts. TP53 mutation led to a decreased 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 and significantly higher relative infiltration of neutrophils and resting memory CD4(+) T cells. Additionally, the IRM index positively correlated with the expression of critical immune checkpoint genes, including PDCD1 (encoding PD‐1) and CD274 (encoding PD‐L1), which was validated in the Nanjing cohort. Furthermore, as an independent prognostic factor, the IRM index was used to establish a nomogram for clinical application. In conclusion, this IRM may serve as a powerful prognostic tool to further optimize LUAD immunotherapy.
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spelling pubmed-87436722022-01-12 Clinical and prognostic implications of an immune‐related risk model based on TP53 status in lung adenocarcinoma Song, Xuming Chen, Qiang Wang, Jifan Mao, Qixing Xia, Wenjie Xu, Lin Jiang, Feng Dong, Gaochao J Cell Mol Med Original Articles 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 remodels the tumour microenvironment to influence tumour progression and prognosis in LUAD. In this study, we developed a 6‐gene immune‐related risk model (IRM) to predict the survival of patients with LUAD in The Cancer Genome Atlas (TCGA) cohort based on TP53 status, and the predictive ability was confirmed in 2 independent cohorts. TP53 mutation led to a decreased 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 and significantly higher relative infiltration of neutrophils and resting memory CD4(+) T cells. Additionally, the IRM index positively correlated with the expression of critical immune checkpoint genes, including PDCD1 (encoding PD‐1) and CD274 (encoding PD‐L1), which was validated in the Nanjing cohort. Furthermore, as an independent prognostic factor, the IRM index was used to establish a nomogram for clinical application. In conclusion, this IRM may serve as a powerful prognostic tool to further optimize LUAD immunotherapy. John Wiley and Sons Inc. 2021-12-08 2022-01 /pmc/articles/PMC8743672/ /pubmed/34877770 http://dx.doi.org/10.1111/jcmm.17097 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Song, Xuming
Chen, Qiang
Wang, Jifan
Mao, Qixing
Xia, Wenjie
Xu, Lin
Jiang, Feng
Dong, Gaochao
Clinical and prognostic implications of an immune‐related risk model based on TP53 status in lung adenocarcinoma
title Clinical and prognostic implications of an immune‐related risk model based on TP53 status in lung adenocarcinoma
title_full Clinical and prognostic implications of an immune‐related risk model based on TP53 status in lung adenocarcinoma
title_fullStr Clinical and prognostic implications of an immune‐related risk model based on TP53 status in lung adenocarcinoma
title_full_unstemmed Clinical and prognostic implications of an immune‐related risk model based on TP53 status in lung adenocarcinoma
title_short Clinical and prognostic implications of an immune‐related risk model based on TP53 status in lung adenocarcinoma
title_sort clinical and prognostic implications of an immune‐related risk model based on tp53 status in lung adenocarcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743672/
https://www.ncbi.nlm.nih.gov/pubmed/34877770
http://dx.doi.org/10.1111/jcmm.17097
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