Journal Article
. 2019 Mar; 42:363-374.
doi: 10.1016/j.ebiom.2019.03.022.

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

Junyu Long 1 Anqiang Wang 2 Yi Bai 1 Jianzhen Lin 1 Xu Yang 1 Dongxu Wang 1 Xiaobo Yang 1 Yan Jiang 3 Haitao Zhao 4 
Affiliations
  • PMID: 30885723
  •     58 References
  •     103 citations

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 TP53WT and TP53MUT 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).

Keywords: Hepatocellular carcinoma; Immune profile; Immune prognostic model; Mutation; TP53.

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Curr Hepatol Rep, 2021 Apr 06; 19(4). PMID: 33816052    Free PMC article.
Identification and validation of a glycolysis-associated multiomics prognostic model for hepatocellular carcinoma.
Tuo Deng, Qian Ye, +7 authors, Yi Wang.
Aging (Albany NY), 2021 Mar 10; 13(5). PMID: 33686959    Free PMC article.
Development and Validation of a Metabolic Gene-Based Prognostic Signature for Hepatocellular Carcinoma.
Jialei Weng, Chenhao Zhou, +6 authors, Ning Ren.
J Hepatocell Carcinoma, 2021 Apr 08; 8. PMID: 33824863    Free PMC article.
Development and external validation of a composite immune-clinical prognostic model associated with EGFR mutation in East-Asian patients with lung adenocarcinoma.
Chengming Liu, Sufei Zheng, +4 authors, Jie He.
Ther Adv Med Oncol, 2021 Apr 24; 13. PMID: 33889215    Free PMC article.
Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success?
Natalia Georgantzoglou, Stefania Kokkali, Gerasimos Tsourouflis, Stamatios Theocharis.
Cancers (Basel), 2021 May 01; 13(8). PMID: 33918733    Free PMC article.
Review.
A genomic mutation signature predicts the clinical outcomes of immunotherapy and characterizes immunophenotypes in gastrointestinal cancer.
Xi Jiao, Xin Wei, +15 authors, Lin Shen.
NPJ Precis Oncol, 2021 May 06; 5(1). PMID: 33947957    Free PMC article.
A prognostic model based on seven immune-related genes predicts the overall survival of patients with hepatocellular carcinoma.
Qian Yan, Wenjiang Zheng, +5 authors, Xiongwen Wang.
BioData Min, 2021 May 09; 14(1). PMID: 33962640    Free PMC article.
Development and Validation of a Metabolic-related Prognostic Model for Hepatocellular Carcinoma.
Junyu Huo, Liqun Wu, Yunjin Zang.
J Clin Transl Hepatol, 2021 May 20; 9(2). PMID: 34007798    Free PMC article.
Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma.
De-Chen Yu, Xiang-Yi Chen, +8 authors, Jiang-Dong An.
Sci Rep, 2021 May 29; 11(1). PMID: 34045512    Free PMC article.
Identifying Dendritic Cell-Related Genes Through a Co-Expression Network to Construct a 12-Gene Risk-Scoring Model for Predicting Hepatocellular Carcinoma Prognosis.
Chaoyuan Huang, Xiaotao Jiang, +3 authors, Fengbin Liu.
Front Mol Biosci, 2021 Jun 11; 8. PMID: 34109210    Free PMC article.
Comprehensive Profiling Reveals Distinct Microenvironment and Metabolism Characterization of Lung Adenocarcinoma.
Chang Li, Chen Tian, +11 authors, Li Liu.
Front Genet, 2021 Jun 15; 12. PMID: 34122500    Free PMC article.
Construction and Validation of a Reliable Six-Gene Prognostic Signature Based on the TP53 Alteration for Hepatocellular Carcinoma.
Junyu Huo, Liqun Wu, Yunjin Zang.
Front Oncol, 2021 Jun 29; 11. PMID: 34178618    Free PMC article.
Identification of immune-infiltrating cell-related biomarkers in hepatocellular carcinoma based on gene co-expression network analysis.
Yinghui Hou, Guizhi Zhang.
Diagn Pathol, 2021 Jul 06; 16(1). PMID: 34218795    Free PMC article.
The TP53-Related Signature Predicts Immune Cell Infiltration, Therapeutic Response, and Prognosis in Patients With Esophageal Carcinoma.
Hongpan Zhang, Zheng Huang, +7 authors, Feng Li.
Front Genet, 2021 Jul 09; 12. PMID: 34234806    Free PMC article.
Shaping Immune Responses in the Tumor Microenvironment of Ovarian Cancer.
Xin Luo, Jing Xu, Jianhua Yu, Ping Yi.
Front Immunol, 2021 Jul 13; 12. PMID: 34248988    Free PMC article.
Review.
Bioinformatics-Based Identification of Tumor Microenvironment-Related Prognostic Genes in Pancreatic Cancer.
Shaojie Chen, Feifei Huang, +5 authors, Kaihong Huang.
Front Genet, 2021 Jul 20; 12. PMID: 34276760    Free PMC article.
Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy.
Junyu Long, Dongxu Wang, +8 authors, Haitao Zhao.
BMC Med, 2021 Jul 22; 19(1). PMID: 34284787    Free PMC article.
A novel recurrence-associated metabolic prognostic model for risk stratification and therapeutic response prediction in patients with stage I lung adenocarcinoma.
Chengming Liu, Sihui Wang, +7 authors, Jie He.
Cancer Biol Med, 2021 Apr 16;. PMID: 33856140    Free PMC article.
Immunological Value of Prognostic Signature Based on Cancer Stem Cell Characteristics in Hepatocellular Carcinoma.
Qianhui Xu, Hao Xu, Shaohuai Chen, Wen Huang.
Front Cell Dev Biol, 2021 Aug 20; 9. PMID: 34409040    Free PMC article.
Biomarkers and Future Perspectives for Hepatocellular Carcinoma Immunotherapy.
Yuqing He, Mengyao Lu, +3 authors, Yuan Chen.
Front Oncol, 2021 Sep 24; 11. PMID: 34552872    Free PMC article.
Review.
Identification and Validation of a Nine-Gene Amino Acid Metabolism-Related Risk Signature in HCC.
Yajuan Zhao, Junli Zhang, +2 authors, Keshu Xu.
Front Cell Dev Biol, 2021 Sep 25; 9. PMID: 34557495    Free PMC article.
A Seven-Gene Signature to Predict Prognosis of Patients With Hepatocellular Carcinoma.
Junli Wang, Qi Zhang, +5 authors, Xueli Bai.
Front Genet, 2021 Oct 05; 12. PMID: 34603388    Free PMC article.
Novel immune-related signature for risk stratification and prognosis in prostatic adenocarcinoma.
Hai-Bo Zhao, Yan-Ru Zeng, +8 authors, Chin-Lee Wu.
Cancer Sci, 2021 Jul 13; 112(10). PMID: 34252262    Free PMC article.
Development and Validation of a Gene Mutation-Associated Nomogram for Hepatocellular Carcinoma Patients From Four Countries.
Tingping Huang, Tao Yan, Gonghai Chen, Chunqing Zhang.
Front Genet, 2021 Oct 09; 12. PMID: 34621291    Free PMC article.
The Prognostic Model Based on Tumor Cell Evolution Trajectory Reveals a Different Risk Group of Hepatocellular Carcinoma.
Haoren Wang, Shizhe Yu, +6 authors, Zhiyong Yu.
Front Cell Dev Biol, 2021 Oct 19; 9. PMID: 34660596    Free PMC article.
Identification of Gene-Set Signature in Early-Stage Hepatocellular Carcinoma and Relevant Immune Characteristics.
Qijie Zhao, Rawiwan Wongpoomchai, +2 authors, Chalermchai Pilapong.
Front Oncol, 2021 Nov 09; 11. PMID: 34745960    Free PMC article.
Identification of SLITRK6 as a Novel Biomarker in hepatocellular carcinoma by comprehensive bioinformatic analysis.
Xudong Liu, Yajie Liu, +11 authors, Lei Wang.
Biochem Biophys Rep, 2021 Nov 11; 28. PMID: 34754951    Free PMC article.
Akt inhibitor augments anti-proliferative efficacy of a dual mTORC1/2 inhibitor by FOXO3a activation in p53 mutated hepatocarcinoma cells.
Tapas Patra, Keith Meyer, +2 authors, Ranjit Ray.
Cell Death Dis, 2021 Nov 12; 12(11). PMID: 34759291    Free PMC article.
Development and validation of a prognostic nomogram model for Chinese patients with primary small cell carcinoma of the esophagus.
Dong-Yun Zhang, Gai-Rong Huang, +8 authors, Li-Dong Wang.
World J Clin Cases, 2021 Nov 18; 9(30). PMID: 34786384    Free PMC article.
Identification of Mutator-Derived lncRNA Signatures of Genomic Instability for Promoting the Clinical Outcome in Hepatocellular Carcinoma.
Xiaolong Tang, Yandong Miao, +3 authors, Denghai Mi.
Comput Math Methods Med, 2021 Nov 30; 2021. PMID: 34840594    Free PMC article.
Identification of a Liver Progenitor Cell-Related Genes Signature Predicting Overall Survival for Hepatocellular Carcinoma.
Xiaoyong Li, Jiaqong Lin, +2 authors, Jintang Xia.
Technol Cancer Res Treat, 2021 Dec 07; 20. PMID: 34866477    Free PMC article.
Avoiding Absolute Quantification Trap: A Novel Predictive Signature of Clinical Benefit to Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer.
Chengming Liu, Sihui Wang, +7 authors, Jie He.
Front Immunol, 2021 Dec 07; 12. PMID: 34868057    Free PMC article.
Exploring the Mechanisms of Arsenic Trioxide (Pishuang) in Hepatocellular Carcinoma Based on Network Pharmacology.
Xinmiao Wang, Luchang Cao, +7 authors, Jie Li.
Evid Based Complement Alternat Med, 2021 Dec 10; 2021. PMID: 34880920    Free PMC article.
A Novel Nine-Gene Signature Associated With Immune Infiltration for Predicting Prognosis in Hepatocellular Carcinoma.
Rongqiang Liu, ZeKun Jiang, +3 authors, Guoying Wang.
Front Genet, 2021 Dec 18; 12. PMID: 34917126    Free PMC article.
Establishment of A Nomogram for Predicting the Prognosis of Soft Tissue Sarcoma Based on Seven Glycolysis-Related Gene Risk Score.
Yuhang Liu, Changjiang Liu, +2 authors, Aixi Yu.
Front Genet, 2021 Dec 21; 12. PMID: 34925434    Free PMC article.
GDI2 is a novel diagnostic and prognostic biomarker in hepatocellular carcinoma.
Wen Zhang, Zhongjian Liu, +7 authors, Zhiwei Sun.
Aging (Albany NY), 2021 Dec 12; 13(23). PMID: 34894398    Free PMC article.
Predictive Biomarkers for Checkpoint Inhibitor-Based Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?
Alessandro Rizzo, Angela Dalia Ricci, +4 authors, Giovanni Brandi.
Front Oncol, 2022 Jan 04; 11. PMID: 34976841    Free PMC article.
Review.
High expression of Ran binding protein 1 predicts poor outcomes in hepatocellular carcinoma patients: a Cancer Genome Atlas database analysis.
Zhengxiao Wei, Xiaoqiong Duan, +2 authors, Yu Wang.
J Gastrointest Oncol, 2022 Jan 25; 12(6). PMID: 35070423    Free PMC article.
Comprehensive analysis of N6-methyladenosine -related long non-coding RNAs and immune cell infiltration in hepatocellular carcinoma.
Zhong Lin Yu, Zheng Ming Zhu.
Bioengineered, 2021 May 07; 12(1). PMID: 33955330    Free PMC article.
A united risk model of 11 immune‑related gene pairs and clinical stage for prediction of overall survival in clear cell renal cell carcinoma patients.
Zijia Tao, Enchong Zhang, +3 authors, Xiaonan Chen.
Bioengineered, 2021 Jul 27; 12(1). PMID: 34304692    Free PMC article.
Characterization of diagnostic and prognostic significance of cell cycle-linked genes in hepatocellular carcinoma.
Jukun Wang, Yu Li, +3 authors, Tao Luo.
Transl Cancer Res, 2022 Feb 05; 10(11). PMID: 35116320    Free PMC article.
Establishment of a prognostic model for predicting short-term disease-free survival in cases of hepatitis B-related hepatocellular carcinoma with the TP53 249Ser mutation in southern China.
Wei Qin, Chuangye Han, +13 authors, Tao Peng.
Transl Cancer Res, 2020 Aug 01; 9(8). PMID: 35117817    Free PMC article.
A Novel Prognostic Signature for Survival Prediction and Immune Implication Based on SARS-CoV-2-Related Genes in Kidney Renal Clear Cell Carcinoma.
Yongbiao Huang, Sheng Chen, +5 authors, Xianglin Yuan.
Front Bioeng Biotechnol, 2022 Feb 11; 9. PMID: 35141213    Free PMC article.
Ferroptosis Regulator Modification Patterns and Tumor Microenvironment Immune Infiltration Characterization in Hepatocellular Carcinoma.
Dong-Li Liu, Ming-Yao Wu, Tie-Ning Zhang, Chun-Gang Wang.
Front Mol Biosci, 2022 Feb 15; 9. PMID: 35155577    Free PMC article.
UBE2T-mediated Akt ubiquitination and Akt/β-catenin activation promotes hepatocellular carcinoma development by increasing pyrimidine metabolism.
Zhenru Zhu, Chuanhui Cao, +4 authors, Jingyuan Sun.
Cell Death Dis, 2022 Feb 17; 13(2). PMID: 35169125    Free PMC article.
A mutation-based gene set predicts survival benefit after immunotherapy across multiple cancers and reveals the immune response landscape.
Junyu Long, Dongxu Wang, +9 authors, Haitao Zhao.
Genome Med, 2022 Feb 25; 14(1). PMID: 35197093    Free PMC article.
A 1p/19q Codeletion-Associated Immune Signature for Predicting Lower Grade Glioma Prognosis.
Jie Xu, Fang Liu, Yuntao Li, Liang Shen.
Cell Mol Neurobiol, 2020 Sep 08; 42(3). PMID: 32894375
Immune-related lncRNA signature delineates an immune-excluded subtype of liver cancer with unfavorable clinical outcomes.
Yawei Chen, Leying Xi, +2 authors, Tianmei Zeng.
J Clin Lab Anal, 2022 Jan 19; 36(3). PMID: 35040184    Free PMC article.
Comprehensive characterization of m6A methylation and its impact on prognosis, genome instability, and tumor microenvironment in hepatocellular carcinoma.
Tengfei Yin, Lang Zhao, Shukun Yao.
BMC Med Genomics, 2022 Mar 10; 15(1). PMID: 35260168    Free PMC article.
Biomarkers and Genetic Markers of Hepatocellular Carcinoma and Cholangiocarcinoma-What Do We Already Know.
Jacek Baj, Łukasz Bryliński, +8 authors, Piero Portincasa.
Cancers (Basel), 2022 Mar 26; 14(6). PMID: 35326644    Free PMC article.
Review.
TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types.
Jia-Zheng Cao, Gao-Sheng Yao, +5 authors, Jin-Huan Wei.
Aging (Albany NY), 2022 Mar 29; 14(6). PMID: 35344507    Free PMC article.
Macrotrabecular-Massive Hepatocellular Carcinoma: What Should We Know?
Xiaoming Li, Qiandong Yao, +4 authors, Ping Cai.
J Hepatocell Carcinoma, 2022 May 14; 9. PMID: 35547829    Free PMC article.
Review.
Prognostic Characteristics and Immune Effects of N6-Methyladenosine and 5-Methylcytosine-Related Regulatory Factors in Clear Cell Renal Cell Carcinoma.
Lei Li, Zijia Tao, +4 authors, Xiaonan Chen.
Front Genet, 2022 May 17; 13. PMID: 35571068    Free PMC article.
PI3K/AKT/mTOR Pathway-Associated Genes Reveal a Putative Prognostic Signature Correlated with Immune Infiltration in Hepatocellular Carcinoma.
Zhihuai Wang, Adeel Ur Rehman, +2 authors, Siyuan Wu.
Dis Markers, 2022 May 21; 2022. PMID: 35592706    Free PMC article.
N6-methyladenosine methylation modification patterns reveal immune profiling in pancreatic adenocarcinoma.
Hao Xu, Lu Yin, +2 authors, Rujun Xu.
Cancer Cell Int, 2022 May 24; 22(1). PMID: 35606813