GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment
Abstract Background Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment of lung adenocarcinoma (LUAD) and are often associated with poorer clinical outcomes. This study aimed to screen for CAF-specific genes that could serve as promising therapeutic targets for LUA...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12920-024-01832-8 |
| _version_ | 1797246967351345152 |
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| author | Ying Bai Tao Han Yunjia Dong Chao Liang Lu Gao Yafeng Liu Jiawei Zhou Jianqiang Guo Deyong Ge Jing Wu Dong Hu |
| author_facet | Ying Bai Tao Han Yunjia Dong Chao Liang Lu Gao Yafeng Liu Jiawei Zhou Jianqiang Guo Deyong Ge Jing Wu Dong Hu |
| author_sort | Ying Bai |
| collection | DOAJ |
| description | Abstract Background Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment of lung adenocarcinoma (LUAD) and are often associated with poorer clinical outcomes. This study aimed to screen for CAF-specific genes that could serve as promising therapeutic targets for LUAD. Methods We established a single-cell transcriptional profile of LUAD, focusing on genetic changes in fibroblasts. Next, we identified key genes associated with fibroblasts through weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis. Then, we evaluated the relationship between glutathione peroxidase 8 (GPX8) and clinical features in multiple independent LUAD cohorts. Furthermore, we analyzed immune infiltration to shed light on the relationship between GPX8 immune microenvironment remodeling. For clinical treatment, we used the tumor immune dysfunction and exclusion (TIDE) algorithm to assess the immunotherapy prediction efficiency of GPX8. After that, we screened potential therapeutic drugs for LUAD by the connectivity map (cMAP). Finally, we conducted a cell trajectory analysis of GPX8+ CAFs to show their unique function. Results Fibroblasts were found to be enriched in tumor tissues. Then we identified GPX8 as a key gene associated with CAFs through comprehensive bioinformatics analysis. Further analysis across multiple LUAD cohorts demonstrated the relationship between GPX8 and poor prognosis. Additionally, we found that GPX8 played a role in inducing the formation of an immunosuppressive microenvironment. The TIDE method indicated that patients with low GPX8 expression were more likely to be responsive to immunotherapy. Using the cMAP, we identified beta-CCP as a potential drug-related to GPX8. Finally, cell trajectory analysis provided insights into the dynamic process of GPX8+ CAFs formation. Conclusions This study elucidates the association between GPX8+ CAFs and poor prognosis, as well as the induction of immunosuppressive formation in LUAD. These findings suggest that targeting GPX8+ CAFs could potentially serve as a therapeutic strategy for the treatment of LUAD. |
| first_indexed | 2024-04-24T19:51:12Z |
| format | Article |
| id | doaj.art-f2b705546e164e1aa15e60cdc8e34017 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-24T19:51:12Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-f2b705546e164e1aa15e60cdc8e340172024-03-24T12:36:44ZengBMCBMC Medical Genomics1755-87942024-03-0117111710.1186/s12920-024-01832-8GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironmentYing Bai0Tao Han1Yunjia Dong2Chao Liang3Lu Gao4Yafeng Liu5Jiawei Zhou6Jianqiang Guo7Deyong Ge8Jing Wu9Dong Hu10Key Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologyKey Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and TechnologyKey Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and TechnologyKey Laboratory of Industrial Dust Prevention and Control & Occupational Safety and Health of the Ministry of Education, Anhui University of Science and TechnologyAbstract Background Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment of lung adenocarcinoma (LUAD) and are often associated with poorer clinical outcomes. This study aimed to screen for CAF-specific genes that could serve as promising therapeutic targets for LUAD. Methods We established a single-cell transcriptional profile of LUAD, focusing on genetic changes in fibroblasts. Next, we identified key genes associated with fibroblasts through weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis. Then, we evaluated the relationship between glutathione peroxidase 8 (GPX8) and clinical features in multiple independent LUAD cohorts. Furthermore, we analyzed immune infiltration to shed light on the relationship between GPX8 immune microenvironment remodeling. For clinical treatment, we used the tumor immune dysfunction and exclusion (TIDE) algorithm to assess the immunotherapy prediction efficiency of GPX8. After that, we screened potential therapeutic drugs for LUAD by the connectivity map (cMAP). Finally, we conducted a cell trajectory analysis of GPX8+ CAFs to show their unique function. Results Fibroblasts were found to be enriched in tumor tissues. Then we identified GPX8 as a key gene associated with CAFs through comprehensive bioinformatics analysis. Further analysis across multiple LUAD cohorts demonstrated the relationship between GPX8 and poor prognosis. Additionally, we found that GPX8 played a role in inducing the formation of an immunosuppressive microenvironment. The TIDE method indicated that patients with low GPX8 expression were more likely to be responsive to immunotherapy. Using the cMAP, we identified beta-CCP as a potential drug-related to GPX8. Finally, cell trajectory analysis provided insights into the dynamic process of GPX8+ CAFs formation. Conclusions This study elucidates the association between GPX8+ CAFs and poor prognosis, as well as the induction of immunosuppressive formation in LUAD. These findings suggest that targeting GPX8+ CAFs could potentially serve as a therapeutic strategy for the treatment of LUAD.https://doi.org/10.1186/s12920-024-01832-8Lung adenocarcinomaGPX8Cancer-associated fibroblastsPrognosisImmunosuppressive microenvironment |
| spellingShingle | Ying Bai Tao Han Yunjia Dong Chao Liang Lu Gao Yafeng Liu Jiawei Zhou Jianqiang Guo Deyong Ge Jing Wu Dong Hu GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment BMC Medical Genomics Lung adenocarcinoma GPX8 Cancer-associated fibroblasts Prognosis Immunosuppressive microenvironment |
| title | GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment |
| title_full | GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment |
| title_fullStr | GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment |
| title_full_unstemmed | GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment |
| title_short | GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment |
| title_sort | gpx8 cancer associated fibroblast as a cancer promoting factor in lung adenocarcinoma is related to the immunosuppressive microenvironment |
| topic | Lung adenocarcinoma GPX8 Cancer-associated fibroblasts Prognosis Immunosuppressive microenvironment |
| url | https://doi.org/10.1186/s12920-024-01832-8 |
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