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Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes

BACKGROUND: L-tryptophan (Trp) metabolism involved in mediating tumour development and immune suppression. However, comprehensive analysis of the role of the Trp metabolism pathway is still a challenge. METHODS: We downloaded Trp metabolism-related genes’ expression data from different public databa...

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Autores principales: Xue, Chen, Gu, Xinyu, Zhao, Yalei, Jia, Junjun, Zheng, Qiuxian, Su, Yuanshuai, Bao, Zhengyi, Lu, Juan, Li, Lanjuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552452/
https://www.ncbi.nlm.nih.gov/pubmed/36217206
http://dx.doi.org/10.1186/s12935-022-02730-8
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author Xue, Chen
Gu, Xinyu
Zhao, Yalei
Jia, Junjun
Zheng, Qiuxian
Su, Yuanshuai
Bao, Zhengyi
Lu, Juan
Li, Lanjuan
author_facet Xue, Chen
Gu, Xinyu
Zhao, Yalei
Jia, Junjun
Zheng, Qiuxian
Su, Yuanshuai
Bao, Zhengyi
Lu, Juan
Li, Lanjuan
author_sort Xue, Chen
collection PubMed
description BACKGROUND: L-tryptophan (Trp) metabolism involved in mediating tumour development and immune suppression. However, comprehensive analysis of the role of the Trp metabolism pathway is still a challenge. METHODS: We downloaded Trp metabolism-related genes’ expression data from different public databases, including TCGA, Gene Expression Omnibus (GEO) and Hepatocellular Carcinoma Database (HCCDB). And we identified two metabolic phenotypes using the ConsensusClusterPlus package. Univariate regression analysis and lasso Cox regression analysis were used to establish a risk model. CIBERSORT and Tracking of Indels by DEcomposition (TIDE) analyses were adopted to assess the infiltration abundance of immune cells and tumour immune escape. RESULTS: We identified two metabolic phenotypes, and patients in Cluster 2 (C2) had a better prognosis than those in Cluster 1 (C1). The distribution of clinical features between the metabolic phenotypes showed that patients in C1 tended to have higher T stage, stage, grade, and death probability than those of patients in C2. Additionally, we screened 739 differentially expressed genes (DEGs) between the C1 and C2. We generated a ten-gene risk model based on the DEGs, and the area under the curve (AUC) values of the risk model for predicting overall survival. Patients in the low-risk subgroup tended to have a significantly longer overall survival than that of those in the high-risk group. Moreover, univariate analysis indicated that the risk model was significantly correlated with overall survival. Multivariate analysis showed that the risk model remained an independent risk factor in hepatocellular carcinoma (p < 0.0001). CONCLUSIONS: We identified two metabolic phenotypes based on genes of the Trp metabolism pathway, and we established a risk model that could be used for predicting prognosis and guiding immunotherapy in patients with hepatocellular carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02730-8.
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spelling pubmed-95524522022-10-12 Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes Xue, Chen Gu, Xinyu Zhao, Yalei Jia, Junjun Zheng, Qiuxian Su, Yuanshuai Bao, Zhengyi Lu, Juan Li, Lanjuan Cancer Cell Int Research BACKGROUND: L-tryptophan (Trp) metabolism involved in mediating tumour development and immune suppression. However, comprehensive analysis of the role of the Trp metabolism pathway is still a challenge. METHODS: We downloaded Trp metabolism-related genes’ expression data from different public databases, including TCGA, Gene Expression Omnibus (GEO) and Hepatocellular Carcinoma Database (HCCDB). And we identified two metabolic phenotypes using the ConsensusClusterPlus package. Univariate regression analysis and lasso Cox regression analysis were used to establish a risk model. CIBERSORT and Tracking of Indels by DEcomposition (TIDE) analyses were adopted to assess the infiltration abundance of immune cells and tumour immune escape. RESULTS: We identified two metabolic phenotypes, and patients in Cluster 2 (C2) had a better prognosis than those in Cluster 1 (C1). The distribution of clinical features between the metabolic phenotypes showed that patients in C1 tended to have higher T stage, stage, grade, and death probability than those of patients in C2. Additionally, we screened 739 differentially expressed genes (DEGs) between the C1 and C2. We generated a ten-gene risk model based on the DEGs, and the area under the curve (AUC) values of the risk model for predicting overall survival. Patients in the low-risk subgroup tended to have a significantly longer overall survival than that of those in the high-risk group. Moreover, univariate analysis indicated that the risk model was significantly correlated with overall survival. Multivariate analysis showed that the risk model remained an independent risk factor in hepatocellular carcinoma (p < 0.0001). CONCLUSIONS: We identified two metabolic phenotypes based on genes of the Trp metabolism pathway, and we established a risk model that could be used for predicting prognosis and guiding immunotherapy in patients with hepatocellular carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02730-8. BioMed Central 2022-10-10 /pmc/articles/PMC9552452/ /pubmed/36217206 http://dx.doi.org/10.1186/s12935-022-02730-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Xue, Chen
Gu, Xinyu
Zhao, Yalei
Jia, Junjun
Zheng, Qiuxian
Su, Yuanshuai
Bao, Zhengyi
Lu, Juan
Li, Lanjuan
Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes
title Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes
title_full Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes
title_fullStr Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes
title_full_unstemmed Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes
title_short Prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes
title_sort prediction of hepatocellular carcinoma prognosis and immunotherapeutic effects based on tryptophan metabolism-related genes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552452/
https://www.ncbi.nlm.nih.gov/pubmed/36217206
http://dx.doi.org/10.1186/s12935-022-02730-8
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