Development and validation of a TP53-associated immune prognostic model for hepatocellular carcinoma

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Abstract

Background

TP53 mutation is the most common mutation in hepatocellular carcinoma (HCC), and it affects the progression and prognosis of HCC. We investigated how TP53 mutation regulates the HCC immunophenotype and thus affects the prognosis of HCC.

Methods

We investigated TP53 mutation status and RNA expression in different populations and platforms and developed an immune prognostic model (IPM) based on immune-related genes that were differentially expressed between TP53 ^WT and TP53 ^MUT HCC samples. Then, the influence of the IPM on the immune microenvironment in HCC was comprehensively analysed.

Findings

TP53 mutation resulted in the downregulation of the immune response in HCC. Thirty-seven of the 312 immune response-related genes were differentially expressed based on TP53 mutation status. An IPM was established and validated based on 865 patients with HCC to differentiate patients with a low or high risk of poor survival. A nomogram was also established for clinical application. Functional enrichment analysis showed that the humoral immune response and immune system diseases pathway represented the major function and pathway, respectively, related to the IPM genes. Moreover, we found that the patients in the high-risk group had higher fractions of T cells follicular helper, T cells regulatory (Tregs) and macrophages M0 and presented higher expression of CTLA-4, PD-1 and TIM-3 than the low-risk group.

Interpretation

TP53 mutation is strongly related to the immune microenvironment in HCC. Our IPM, which is sensitive to TP53 mutation status, may have important implications for identifying subgroups of HCC patients with low or high risk of unfavourable survival.

Fund

This work was supported by the International Science and Technology Cooperation Projects (2016YFE0107100), the Capital Special Research Project for Health Development (2014-2-4012), the Beijing Natural Science Foundation (L172055 and 7192158), the National Ten Thousand Talent Program, the Fundamental Research Funds for the Central Universities (3332018032), and the CAMS Innovation Fund for Medical Science (CIFMS) (2017-I2M-4-003 and 2018-I2M-3-001).

Related collections

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Author and article information

Contributors

Haitao Zhao

Journal

Journal ID (nlm-ta): EBioMedicine

Journal ID (iso-abbrev): EBioMedicine

Title: EBioMedicine

Publisher: Elsevier

ISSN (Electronic): 2352-3964

Publication date PMC-release: 16 March 2019

Publication date Collection: April 2019

Publication date (Electronic): 16 March 2019

Volume: 42

Pages: 363-374

Affiliations

[a ]Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

[b ]Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, China

[c ]OrigiMed Inc., Shanghai, China

Author notes

[* ]Corresponding author. zhaoht@ 123456pumch.cn

[1]

These authors contributed equally to this work.

Article

Publisher ID: S2352-3964(19)30162-8

DOI: 10.1016/j.ebiom.2019.03.022

PMC ID: 6491941

PubMed ID: 30885723

SO-VID: 29b133ec-878c-4ec2-83a4-a51adfd0de2e

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 19 October 2018

Date revision received : 7 March 2019

Date accepted : 8 March 2019

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