Retinoic Acid Metabolism-Related Enzyme Signature Identified Prognostic and Immune Characteristics in Sarcoma
Growing evidence indicates a link between retinoic acid (RA) metabolism and sarcoma progression or immunity in laboratory studies. However, a comprehensive analysis of RA abnormality in the sarcoma population is still lacking. Herein, we systematically analyzed the molecular features of 19 retinoic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.780951/full |
| _version_ | 1818082902996418560 |
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| author | HuaiYuan Xu JinXin Hu YiJiang Song HongMin Chen YanYang Xu ChuangZhong Deng Hao Wu GuoHui Song JinChang Lu QinLian Tang LiangPing Xia Jin Wang XiaoJun Zhu |
| author_facet | HuaiYuan Xu JinXin Hu YiJiang Song HongMin Chen YanYang Xu ChuangZhong Deng Hao Wu GuoHui Song JinChang Lu QinLian Tang LiangPing Xia Jin Wang XiaoJun Zhu |
| author_sort | HuaiYuan Xu |
| collection | DOAJ |
| description | Growing evidence indicates a link between retinoic acid (RA) metabolism and sarcoma progression or immunity in laboratory studies. However, a comprehensive analysis of RA abnormality in the sarcoma population is still lacking. Herein, we systematically analyzed the molecular features of 19 retinoic acid metabolism-related enzymes and sarcoma patients’ clinical information based on TCGA/TARGET/GSE datasets. We identified two RA expression subtypes, which were related to distinct clinical survival outcomes and exhibited different biological features. Gene set enrichment analysis indicated a set of immune pathways were enriched in G1 while oncogenic pathways were enriched in G2. Immune cell infiltration analysis using the TIMER algorithm revealed more CD4+ and CD8+ T cell infiltration in G1 subgroups than in G2. Moreover, we generated a seven genes signature to predict the RA metabolism index based on the LASSO-penalized Cox regression model. Survival analysis demonstrated the significant prognostic differences between high- and low-risk groups among different bone and soft tissue datasets. A higher risk index was associated with less T cell CD8+ infiltration. The predictive ability of the RA risk score was validated in 71 bone or soft tissue sarcoma clinical samples. These results indicated that RA-based classification could distinguish sarcoma patients with different clinical outcomes and immune statuses, which may help to explore better treatment decision-making for sarcoma patients. |
| first_indexed | 2024-12-10T19:29:29Z |
| format | Article |
| id | doaj.art-889568d0739f47a4b3d473736d41f828 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-10T19:29:29Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-889568d0739f47a4b3d473736d41f8282022-12-22T01:36:17ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-02-01910.3389/fcell.2021.780951780951Retinoic Acid Metabolism-Related Enzyme Signature Identified Prognostic and Immune Characteristics in SarcomaHuaiYuan Xu0JinXin Hu1YiJiang Song2HongMin Chen3YanYang Xu4ChuangZhong Deng5Hao Wu6GuoHui Song7JinChang Lu8QinLian Tang9LiangPing Xia10Jin Wang11XiaoJun Zhu12Department of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaVIP Department, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Musculoskeletal Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaGrowing evidence indicates a link between retinoic acid (RA) metabolism and sarcoma progression or immunity in laboratory studies. However, a comprehensive analysis of RA abnormality in the sarcoma population is still lacking. Herein, we systematically analyzed the molecular features of 19 retinoic acid metabolism-related enzymes and sarcoma patients’ clinical information based on TCGA/TARGET/GSE datasets. We identified two RA expression subtypes, which were related to distinct clinical survival outcomes and exhibited different biological features. Gene set enrichment analysis indicated a set of immune pathways were enriched in G1 while oncogenic pathways were enriched in G2. Immune cell infiltration analysis using the TIMER algorithm revealed more CD4+ and CD8+ T cell infiltration in G1 subgroups than in G2. Moreover, we generated a seven genes signature to predict the RA metabolism index based on the LASSO-penalized Cox regression model. Survival analysis demonstrated the significant prognostic differences between high- and low-risk groups among different bone and soft tissue datasets. A higher risk index was associated with less T cell CD8+ infiltration. The predictive ability of the RA risk score was validated in 71 bone or soft tissue sarcoma clinical samples. These results indicated that RA-based classification could distinguish sarcoma patients with different clinical outcomes and immune statuses, which may help to explore better treatment decision-making for sarcoma patients.https://www.frontiersin.org/articles/10.3389/fcell.2021.780951/fullretinoic acid metabolismsarcomaLASSO-penalized cox regressionimmuneCD8+ T cell |
| spellingShingle | HuaiYuan Xu JinXin Hu YiJiang Song HongMin Chen YanYang Xu ChuangZhong Deng Hao Wu GuoHui Song JinChang Lu QinLian Tang LiangPing Xia Jin Wang XiaoJun Zhu Retinoic Acid Metabolism-Related Enzyme Signature Identified Prognostic and Immune Characteristics in Sarcoma Frontiers in Cell and Developmental Biology retinoic acid metabolism sarcoma LASSO-penalized cox regression immune CD8+ T cell |
| title | Retinoic Acid Metabolism-Related Enzyme Signature Identified Prognostic and Immune Characteristics in Sarcoma |
| title_full | Retinoic Acid Metabolism-Related Enzyme Signature Identified Prognostic and Immune Characteristics in Sarcoma |
| title_fullStr | Retinoic Acid Metabolism-Related Enzyme Signature Identified Prognostic and Immune Characteristics in Sarcoma |
| title_full_unstemmed | Retinoic Acid Metabolism-Related Enzyme Signature Identified Prognostic and Immune Characteristics in Sarcoma |
| title_short | Retinoic Acid Metabolism-Related Enzyme Signature Identified Prognostic and Immune Characteristics in Sarcoma |
| title_sort | retinoic acid metabolism related enzyme signature identified prognostic and immune characteristics in sarcoma |
| topic | retinoic acid metabolism sarcoma LASSO-penalized cox regression immune CD8+ T cell |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.780951/full |
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