A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma
Immunotherapy, such as immune checkpoint inhibitors (ICIs), is a validated strategy for treating lung adenocarcinoma (LUAD) patients. One of the main challenges in ICIs treatment is the lack of efficient biomarkers for predicting response or resistance. Metabolic reprogramming has been proven to rem...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12143 |
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| author | Bo Tang Lanlin Hu Tao Jiang Yunchang Li Huasheng Xu Hang Zhou Mei Lan Ke Xu Jun Yin Chunxia Su Caicun Zhou Chuan Xu |
| author_facet | Bo Tang Lanlin Hu Tao Jiang Yunchang Li Huasheng Xu Hang Zhou Mei Lan Ke Xu Jun Yin Chunxia Su Caicun Zhou Chuan Xu |
| author_sort | Bo Tang |
| collection | DOAJ |
| description | Immunotherapy, such as immune checkpoint inhibitors (ICIs), is a validated strategy for treating lung adenocarcinoma (LUAD) patients. One of the main challenges in ICIs treatment is the lack of efficient biomarkers for predicting response or resistance. Metabolic reprogramming has been proven to remodel the tumor microenvironment, altering the response to ICIs. We constructed a prognostic model as metabolism-related gene (MRG) of four genes by using weighted gene co-expression network analysis (WGCNA), the nonnegative matrix factorization (NMF), and Cox regression analysis of a LUAD dataset (<i>n</i> = 500) from The Cancer Genome Atlas (TCGA), which was validated with three Gene Expression Omnibus (GEO) datasets (<i>n </i>= 442, <i>n </i>= 226 and <i>n</i> = 127). The MRG was constructed based on <i>BIRC5</i>, <i>PLK1</i>, <i>CDKN3</i>, and <i>CYP4B1</i> genes. MRG-high patients had a worse survival probability than MRG-low patients. Furthermore, the MRG-high subgroup was more associated with cell cycle-related pathways; high infiltration of activated memory CD4<sup>+</sup>T cells, M0 macrophages, and neutrophils; and showed better response to ICIs. Contrarily, the MRG-low subgroup was associated with fatty acid metabolism, high infiltration of dendric cells, and resting mast cells, and showed poor response to ICIs. MRG is a promising prognostic index for predicting survival and response to ICIs and other therapeutic agents in LUAD, which might provide insights on strategies with ICIs alone or combined with other agents. |
| first_indexed | 2024-03-09T12:15:57Z |
| format | Article |
| id | doaj.art-8708ff60f873449c950f4bbf2ad82969 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:15:57Z |
| publishDate | 2022-10-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8708ff60f873449c950f4bbf2ad829692023-11-30T22:46:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201214310.3390/ijms232012143A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung AdenocarcinomaBo Tang0Lanlin Hu1Tao Jiang2Yunchang Li3Huasheng Xu4Hang Zhou5Mei Lan6Ke Xu7Jun Yin8Chunxia Su9Caicun Zhou10Chuan Xu11Integrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, ChinaIntegrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, ChinaDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zhengmin Road, Shanghai 200433, ChinaIntegrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, ChinaCollaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application, Guangxi Medical University, Nanning 530021, ChinaIntegrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, ChinaIntegrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, ChinaIntegrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, ChinaIntegrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, ChinaDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zhengmin Road, Shanghai 200433, ChinaDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zhengmin Road, Shanghai 200433, ChinaIntegrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, ChinaImmunotherapy, such as immune checkpoint inhibitors (ICIs), is a validated strategy for treating lung adenocarcinoma (LUAD) patients. One of the main challenges in ICIs treatment is the lack of efficient biomarkers for predicting response or resistance. Metabolic reprogramming has been proven to remodel the tumor microenvironment, altering the response to ICIs. We constructed a prognostic model as metabolism-related gene (MRG) of four genes by using weighted gene co-expression network analysis (WGCNA), the nonnegative matrix factorization (NMF), and Cox regression analysis of a LUAD dataset (<i>n</i> = 500) from The Cancer Genome Atlas (TCGA), which was validated with three Gene Expression Omnibus (GEO) datasets (<i>n </i>= 442, <i>n </i>= 226 and <i>n</i> = 127). The MRG was constructed based on <i>BIRC5</i>, <i>PLK1</i>, <i>CDKN3</i>, and <i>CYP4B1</i> genes. MRG-high patients had a worse survival probability than MRG-low patients. Furthermore, the MRG-high subgroup was more associated with cell cycle-related pathways; high infiltration of activated memory CD4<sup>+</sup>T cells, M0 macrophages, and neutrophils; and showed better response to ICIs. Contrarily, the MRG-low subgroup was associated with fatty acid metabolism, high infiltration of dendric cells, and resting mast cells, and showed poor response to ICIs. MRG is a promising prognostic index for predicting survival and response to ICIs and other therapeutic agents in LUAD, which might provide insights on strategies with ICIs alone or combined with other agents.https://www.mdpi.com/1422-0067/23/20/12143prognostic indexmetabolism-related geneslung adenocarcinomaimmunotherapy |
| spellingShingle | Bo Tang Lanlin Hu Tao Jiang Yunchang Li Huasheng Xu Hang Zhou Mei Lan Ke Xu Jun Yin Chunxia Su Caicun Zhou Chuan Xu A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma International Journal of Molecular Sciences prognostic index metabolism-related genes lung adenocarcinoma immunotherapy |
| title | A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma |
| title_full | A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma |
| title_fullStr | A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma |
| title_full_unstemmed | A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma |
| title_short | A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma |
| title_sort | metabolism related gene prognostic index for prediction of response to immunotherapy in lung adenocarcinoma |
| topic | prognostic index metabolism-related genes lung adenocarcinoma immunotherapy |
| url | https://www.mdpi.com/1422-0067/23/20/12143 |
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