A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma
The therapeutic strategy of Ewing sarcoma (EWS) remains largely unchanged over the past few decades. Hypoxia is reported to have an impact on tumor cell progression and is regarded as a novel potential therapeutic target in tumor treatment. This study aimed at developing a prognostic gene signature...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.908113/full |
| _version_ | 1818218751179358208 |
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| author | Runyi Jiang Jinbo Hu Hongfei Zhou Hongfei Zhou Haifeng Wei Shaohui He Jianru Xiao |
| author_facet | Runyi Jiang Jinbo Hu Hongfei Zhou Hongfei Zhou Haifeng Wei Shaohui He Jianru Xiao |
| author_sort | Runyi Jiang |
| collection | DOAJ |
| description | The therapeutic strategy of Ewing sarcoma (EWS) remains largely unchanged over the past few decades. Hypoxia is reported to have an impact on tumor cell progression and is regarded as a novel potential therapeutic target in tumor treatment. This study aimed at developing a prognostic gene signature based on hypoxia-related genes (HRGs). EWS patients from GSE17674 in the GEO database were analyzed as a training cohort, and differently expressed HRGs between tumor and normal samples were identified. The univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used in this study. A total of 57 EWS patients from the International Cancer Genome Consortium (ICGC) database were set as the validation cohort. A total of 506 differently expressed HRGs between tumor and normal tissues were identified, among which 52 were associated with the prognoses of EWS patients. Based on 52 HRGs, EWS patients were divided into two molecular subgroups with different survival statuses. In addition, a prognostic signature based on 4 HRGs (WSB1, RXYLT1, GLCE and RORA) was constructed, dividing EWS patients into low- and high-risk groups. The 2-, 3- and 5-years area under the receiver operator characteristic curve of this signature was 0.913, 0.97 and 0.985, respectively. It was found that the survival rates of patients in the high-risk group were significantly lower than those in the low-risk group (p < 0.001). The risk level based on the risk score could serve as an independent clinical factor for predicting the survival probabilities of EWS patients. Additionally, antigen-presenting cell (APC) related pathways and T cell co-inhibition were differently activated in two risk groups, which may result in different prognoses. CTLA4 may be an effective immune checkpoint inhibitor to treat EWS patients. All results were verified in the validation cohort. This study constructed 4-HRGs as a novel prognostic marker for predicting survival in EWS patients. |
| first_indexed | 2024-12-12T07:28:44Z |
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| id | doaj.art-31f6bef58a9d479988e130401c79d907 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-12T07:28:44Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-31f6bef58a9d479988e130401c79d9072022-12-22T00:33:04ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-06-011310.3389/fgene.2022.908113908113A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing SarcomaRunyi Jiang0Jinbo Hu1Hongfei Zhou2Hongfei Zhou3Haifeng Wei4Shaohui He5Jianru Xiao6Spinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaSpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaSpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaThe Third Convalescent Department, Hangzhou Sanatorium, Hangzhou, ChinaSpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaSpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaSpinal Tumor Center, Department of Orthopaedic Oncology, No.905 Hospital of PLA Navy, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaThe therapeutic strategy of Ewing sarcoma (EWS) remains largely unchanged over the past few decades. Hypoxia is reported to have an impact on tumor cell progression and is regarded as a novel potential therapeutic target in tumor treatment. This study aimed at developing a prognostic gene signature based on hypoxia-related genes (HRGs). EWS patients from GSE17674 in the GEO database were analyzed as a training cohort, and differently expressed HRGs between tumor and normal samples were identified. The univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used in this study. A total of 57 EWS patients from the International Cancer Genome Consortium (ICGC) database were set as the validation cohort. A total of 506 differently expressed HRGs between tumor and normal tissues were identified, among which 52 were associated with the prognoses of EWS patients. Based on 52 HRGs, EWS patients were divided into two molecular subgroups with different survival statuses. In addition, a prognostic signature based on 4 HRGs (WSB1, RXYLT1, GLCE and RORA) was constructed, dividing EWS patients into low- and high-risk groups. The 2-, 3- and 5-years area under the receiver operator characteristic curve of this signature was 0.913, 0.97 and 0.985, respectively. It was found that the survival rates of patients in the high-risk group were significantly lower than those in the low-risk group (p < 0.001). The risk level based on the risk score could serve as an independent clinical factor for predicting the survival probabilities of EWS patients. Additionally, antigen-presenting cell (APC) related pathways and T cell co-inhibition were differently activated in two risk groups, which may result in different prognoses. CTLA4 may be an effective immune checkpoint inhibitor to treat EWS patients. All results were verified in the validation cohort. This study constructed 4-HRGs as a novel prognostic marker for predicting survival in EWS patients.https://www.frontiersin.org/articles/10.3389/fgene.2022.908113/fullewing sarcomagene signaturehypoxiabiomarkersprognosis |
| spellingShingle | Runyi Jiang Jinbo Hu Hongfei Zhou Hongfei Zhou Haifeng Wei Shaohui He Jianru Xiao A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma Frontiers in Genetics ewing sarcoma gene signature hypoxia biomarkers prognosis |
| title | A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma |
| title_full | A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma |
| title_fullStr | A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma |
| title_full_unstemmed | A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma |
| title_short | A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma |
| title_sort | novel defined hypoxia related gene signature for prognostic prediction of patients with ewing sarcoma |
| topic | ewing sarcoma gene signature hypoxia biomarkers prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.908113/full |
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