A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma
Background: Ubiquitination is medicated by three classes of enzymes and has been proven to involve in multiple cancer biological processes. Moreover, dysregulation of ubiquitination has received a growing body of attention in osteosarcoma (OS) tumorigenesis and treatment. Therefore, our study aimed...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.904448/full |
| _version_ | 1811215025248927744 |
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| author | Nan Wei Nan Wei Gong Chao-yang Gong Chao-yang Zhou Wen-ming Zhou Wen-ming Lei Ze-yuan Lei Ze-yuan Shi Yong-qiang Shi Yong-qiang Zhang Shun-bai Zhang Shun-bai Zhang Kai Zhang Kai Ma Yan-chao Ma Yan-chao Zhang Hai-hong Zhang Hai-hong |
| author_facet | Nan Wei Nan Wei Gong Chao-yang Gong Chao-yang Zhou Wen-ming Zhou Wen-ming Lei Ze-yuan Lei Ze-yuan Shi Yong-qiang Shi Yong-qiang Zhang Shun-bai Zhang Shun-bai Zhang Kai Zhang Kai Ma Yan-chao Ma Yan-chao Zhang Hai-hong Zhang Hai-hong |
| author_sort | Nan Wei |
| collection | DOAJ |
| description | Background: Ubiquitination is medicated by three classes of enzymes and has been proven to involve in multiple cancer biological processes. Moreover, dysregulation of ubiquitination has received a growing body of attention in osteosarcoma (OS) tumorigenesis and treatment. Therefore, our study aimed to identify a ubiquitin-related gene signature for predicting prognosis and immune landscape and constructing OS molecular subtypes.Methods: Therapeutically Applicable Research to Generate Effective Treatments (TARGET) was regarded as the training set through univariate Cox regression, Lasso Cox regression, and multivariate Cox regression. The GSE21257 and GSE39055 served as the validation set to verify the predictive value of the signature. CIBERSORT was performed to show immune infiltration and the immune microenvironment. The NMF algorithm was used to construct OS molecular subtypes.Results: In this study, we developed a ubiquitin-related gene signature including seven genes (UBE2L3, CORO6, DCAF8, DNAI1, FBXL5, UHRF2, and WDR53), and the gene signature had a good performance in predicting prognosis for OS patients (AUC values at 1/3/5 years were 0.957, 0.890, and 0.919). Multivariate Cox regression indicated that the risk score model and prognosis stage were also independent prognostic prediction factors. Moreover, analyses of immune cells and immune-related functions showed a significant difference in different risk score groups and the three clusters. The drug sensitivity suggested that IC50 of proteasome inhibitor (MG-132) showed a notable significance between the risk score groups (p < 0.05). Through the NMF algorithm, we obtained the three clusters, and cluster 3 showed better survival outcomes. The expression of ubiquitin-related genes (CORO6, UBE2L3, FBXL5, DNAI1, and DCAF8) showed an obvious significance in normal and osteosarcoma tissues.Conclusion: We developed a novel ubiquitin-related gene signature which showed better predictive prognostic ability for OS and provided additional information on chemotherapy and immunotherapy. The OS molecular subtypes would also give a useful guide for individualized therapy. |
| first_indexed | 2024-04-12T06:15:27Z |
| format | Article |
| id | doaj.art-e727cee6875b49edb9bdb400584dab44 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T06:15:27Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-e727cee6875b49edb9bdb400584dab442022-12-22T03:44:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.904448904448A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcomaNan Wei0Nan Wei1Gong Chao-yang2Gong Chao-yang3Zhou Wen-ming4Zhou Wen-ming5Lei Ze-yuan6Lei Ze-yuan7Shi Yong-qiang8Shi Yong-qiang9Zhang Shun-bai10Zhang Shun-bai11Zhang Kai12Zhang Kai13Ma Yan-chao14Ma Yan-chao15Zhang Hai-hong16Zhang Hai-hong17Orthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaLanzhou University Second Hospital, Lanzhou, ChinaBackground: Ubiquitination is medicated by three classes of enzymes and has been proven to involve in multiple cancer biological processes. Moreover, dysregulation of ubiquitination has received a growing body of attention in osteosarcoma (OS) tumorigenesis and treatment. Therefore, our study aimed to identify a ubiquitin-related gene signature for predicting prognosis and immune landscape and constructing OS molecular subtypes.Methods: Therapeutically Applicable Research to Generate Effective Treatments (TARGET) was regarded as the training set through univariate Cox regression, Lasso Cox regression, and multivariate Cox regression. The GSE21257 and GSE39055 served as the validation set to verify the predictive value of the signature. CIBERSORT was performed to show immune infiltration and the immune microenvironment. The NMF algorithm was used to construct OS molecular subtypes.Results: In this study, we developed a ubiquitin-related gene signature including seven genes (UBE2L3, CORO6, DCAF8, DNAI1, FBXL5, UHRF2, and WDR53), and the gene signature had a good performance in predicting prognosis for OS patients (AUC values at 1/3/5 years were 0.957, 0.890, and 0.919). Multivariate Cox regression indicated that the risk score model and prognosis stage were also independent prognostic prediction factors. Moreover, analyses of immune cells and immune-related functions showed a significant difference in different risk score groups and the three clusters. The drug sensitivity suggested that IC50 of proteasome inhibitor (MG-132) showed a notable significance between the risk score groups (p < 0.05). Through the NMF algorithm, we obtained the three clusters, and cluster 3 showed better survival outcomes. The expression of ubiquitin-related genes (CORO6, UBE2L3, FBXL5, DNAI1, and DCAF8) showed an obvious significance in normal and osteosarcoma tissues.Conclusion: We developed a novel ubiquitin-related gene signature which showed better predictive prognostic ability for OS and provided additional information on chemotherapy and immunotherapy. The OS molecular subtypes would also give a useful guide for individualized therapy.https://www.frontiersin.org/articles/10.3389/fphar.2022.904448/fullosteosarcomaubiquitinubiquitinationimmunemolecular subtypes |
| spellingShingle | Nan Wei Nan Wei Gong Chao-yang Gong Chao-yang Zhou Wen-ming Zhou Wen-ming Lei Ze-yuan Lei Ze-yuan Shi Yong-qiang Shi Yong-qiang Zhang Shun-bai Zhang Shun-bai Zhang Kai Zhang Kai Ma Yan-chao Ma Yan-chao Zhang Hai-hong Zhang Hai-hong A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma Frontiers in Pharmacology osteosarcoma ubiquitin ubiquitination immune molecular subtypes |
| title | A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma |
| title_full | A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma |
| title_fullStr | A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma |
| title_full_unstemmed | A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma |
| title_short | A ubiquitin-related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma |
| title_sort | ubiquitin related gene signature for predicting prognosis and constructing molecular subtypes in osteosarcoma |
| topic | osteosarcoma ubiquitin ubiquitination immune molecular subtypes |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.904448/full |
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