Cell Differentiation Trajectory-Associated Molecular Classification of Osteosarcoma
This study aims to investigate the differentiation trajectory of osteosarcoma cells and to construct molecular subtypes with their respective characteristics and generate a multi-gene signature for predicting prognosis. Integrated single-cell RNA-sequencing (scRNA-seq) data, bulk RNA-seq data and mi...
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MDPI AG
2021
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oai:doaj.org-article:3aa8d8cf2c884d1b8b18db3b65041fa12021-11-25T17:40:48ZCell Differentiation Trajectory-Associated Molecular Classification of Osteosarcoma10.3390/genes121116852073-4425https://doaj.org/article/3aa8d8cf2c884d1b8b18db3b65041fa12021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1685https://doaj.org/toc/2073-4425This study aims to investigate the differentiation trajectory of osteosarcoma cells and to construct molecular subtypes with their respective characteristics and generate a multi-gene signature for predicting prognosis. Integrated single-cell RNA-sequencing (scRNA-seq) data, bulk RNA-seq data and microarray data from osteosarcoma samples were used for analysis. Via scRNA-seq data, time-related as well as differentiation-related genes were recognized as osteosarcoma tumor stem cell-related genes (OSCGs). In Gene Expression Omnibus (GEO) cohort, osteosarcoma patients were classified into two subtypes based on prognostic OSCGs and it was found that molecular typing successfully predicted overall survival, tumor microenvironment and immune infiltration status. Further, available drugs for influencing osteosarcoma via prognostic OSCGs were revealed. A 3-OSCG-based prognostic risk score signature was generated and by combining other clinic-pathological independent prognostic factor, stage at diagnosis, a nomogram was established to predict individual survival probability. In external independent TARGET cohort, the molecular types, the 3-gene signature as well as nomogram were validated. In conclusion, osteosarcoma cell differentiation occupies a crucial position in many facets, such as tumor prognosis and microenvironment, suggesting promising therapeutic targets for this disease.Ankai XuChao QianJinti LinWei YuJiakang JinBing LiuHuimin TaoMDPI AGarticletumor/cancer stem celldifferentiation trajectorymolecular typingGeneticsQH426-470ENGenes, Vol 12, Iss 1685, p 1685 (2021) |
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tumor/cancer stem cell differentiation trajectory molecular typing Genetics QH426-470 |
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tumor/cancer stem cell differentiation trajectory molecular typing Genetics QH426-470 Ankai Xu Chao Qian Jinti Lin Wei Yu Jiakang Jin Bing Liu Huimin Tao Cell Differentiation Trajectory-Associated Molecular Classification of Osteosarcoma |
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This study aims to investigate the differentiation trajectory of osteosarcoma cells and to construct molecular subtypes with their respective characteristics and generate a multi-gene signature for predicting prognosis. Integrated single-cell RNA-sequencing (scRNA-seq) data, bulk RNA-seq data and microarray data from osteosarcoma samples were used for analysis. Via scRNA-seq data, time-related as well as differentiation-related genes were recognized as osteosarcoma tumor stem cell-related genes (OSCGs). In Gene Expression Omnibus (GEO) cohort, osteosarcoma patients were classified into two subtypes based on prognostic OSCGs and it was found that molecular typing successfully predicted overall survival, tumor microenvironment and immune infiltration status. Further, available drugs for influencing osteosarcoma via prognostic OSCGs were revealed. A 3-OSCG-based prognostic risk score signature was generated and by combining other clinic-pathological independent prognostic factor, stage at diagnosis, a nomogram was established to predict individual survival probability. In external independent TARGET cohort, the molecular types, the 3-gene signature as well as nomogram were validated. In conclusion, osteosarcoma cell differentiation occupies a crucial position in many facets, such as tumor prognosis and microenvironment, suggesting promising therapeutic targets for this disease. |
format |
article |
author |
Ankai Xu Chao Qian Jinti Lin Wei Yu Jiakang Jin Bing Liu Huimin Tao |
author_facet |
Ankai Xu Chao Qian Jinti Lin Wei Yu Jiakang Jin Bing Liu Huimin Tao |
author_sort |
Ankai Xu |
title |
Cell Differentiation Trajectory-Associated Molecular Classification of Osteosarcoma |
title_short |
Cell Differentiation Trajectory-Associated Molecular Classification of Osteosarcoma |
title_full |
Cell Differentiation Trajectory-Associated Molecular Classification of Osteosarcoma |
title_fullStr |
Cell Differentiation Trajectory-Associated Molecular Classification of Osteosarcoma |
title_full_unstemmed |
Cell Differentiation Trajectory-Associated Molecular Classification of Osteosarcoma |
title_sort |
cell differentiation trajectory-associated molecular classification of osteosarcoma |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/3aa8d8cf2c884d1b8b18db3b65041fa1 |
work_keys_str_mv |
AT ankaixu celldifferentiationtrajectoryassociatedmolecularclassificationofosteosarcoma AT chaoqian celldifferentiationtrajectoryassociatedmolecularclassificationofosteosarcoma AT jintilin celldifferentiationtrajectoryassociatedmolecularclassificationofosteosarcoma AT weiyu celldifferentiationtrajectoryassociatedmolecularclassificationofosteosarcoma AT jiakangjin celldifferentiationtrajectoryassociatedmolecularclassificationofosteosarcoma AT bingliu celldifferentiationtrajectoryassociatedmolecularclassificationofosteosarcoma AT huimintao celldifferentiationtrajectoryassociatedmolecularclassificationofosteosarcoma |
_version_ |
1718412097293910016 |