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Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Hepatocellular Carcinoma | Research

Model based on five tumour immune microenvironment-related genes for predicting hepatocellular carcinoma immunotherapy outcomes

Authors: Xinyu Gu, Jun Guan, Jia Xu, Qiuxian Zheng, Chao Chen, Qin Yang, Chunhong Huang, Gang Wang, Haibo Zhou, Zhi Chen, Haihong Zhu

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Background

Although the tumour immune microenvironment is known to significantly influence immunotherapy outcomes, its association with changes in gene expression patterns in hepatocellular carcinoma (HCC) during immunotherapy and its effect on prognosis have not been clarified.

Methods

A total of 365 HCC samples from The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) dataset were stratified into training datasets and verification datasets. In the training datasets, immune-related genes were analysed through univariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO)-Cox analyses to build a prognostic model. The TCGA-LIHC, GSE14520, and Imvigor210 cohorts were subjected to time-dependent receiver operating characteristic (ROC) and Kaplan–Meier survival curve analyses to verify the reliability of the developed model. Finally, single-sample gene set enrichment analysis (ssGSEA) was used to study the underlying molecular mechanisms.

Results

Five immune-related genes (LDHA, PPAT, BFSP1, NR0B1, and PFKFB4) were identified and used to establish the prognostic model for patient response to HCC treatment. ROC curve analysis of the TCGA (training and validation sets) and GSE14520 cohorts confirmed the predictive ability of the five-gene-based model (AUC > 0.6). In addition, ROC and Kaplan–Meier analyses indicated that the model could stratify patients into a low-risk and a high-risk group, wherein the high-risk group exhibited worse prognosis and was less sensitive to immunotherapy than the low-risk group. Functional enrichment analysis predicted potential associations of the five genes with several metabolic processes and oncological signatures.

Conclusions

We established a novel five-gene-based prognostic model based on the tumour immune microenvironment that can predict immunotherapy efficacy in HCC patients.
Appendix
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Metadata
Title
Model based on five tumour immune microenvironment-related genes for predicting hepatocellular carcinoma immunotherapy outcomes
Authors
Xinyu Gu
Jun Guan
Jia Xu
Qiuxian Zheng
Chao Chen
Qin Yang
Chunhong Huang
Gang Wang
Haibo Zhou
Zhi Chen
Haihong Zhu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-020-02691-4

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