Integrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma
Abstract Osteosarcoma (OSA) is a primary bone malignancy characterized by its aggressive nature and high propensity for metastasis. Despite advancements in multimodal therapies, the clinical outcomes for OSA patients remain suboptimal, necessitating deeper molecular insights for improved therapeutic...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2024-11-01
|
| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-024-01523-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849221117191913472 |
|---|---|
| author | Dongan He Xiaoqian Che Haiming Zhang Jiandong Guo Lei Cai Jian Li Jinxi Zhang Xin Jin Jianfeng Wang |
| author_facet | Dongan He Xiaoqian Che Haiming Zhang Jiandong Guo Lei Cai Jian Li Jinxi Zhang Xin Jin Jianfeng Wang |
| author_sort | Dongan He |
| collection | DOAJ |
| description | Abstract Osteosarcoma (OSA) is a primary bone malignancy characterized by its aggressive nature and high propensity for metastasis. Despite advancements in multimodal therapies, the clinical outcomes for OSA patients remain suboptimal, necessitating deeper molecular insights for improved therapeutic strategies. Here, we employed single-cell RNA sequencing (scRNA-seq) to elucidate the cellular heterogeneity and transcriptional dynamics of OSA tumors. Our study identified eleven distinct tumor cell subpopulations, including osteoblastic, chondroblastic, and myeloid lineages, each exhibiting unique transcriptional profiles associated with disease progression and metastasis. Epithelial-mesenchymal transition (EMT) emerged as a critical process driving aggressive phenotypes, supported by gene set enrichment analyses (GSVA) and transcription factor regulatory network analyses. Integration of copy number variation (CNV) data highlighted genomic alterations in osteoblastic and chondroblastic cells, implicating potential therapeutic targets. Furthermore, immune cell infiltration analyses revealed distinct immune profiles across OSA subtypes, correlating with tumor mutational burden (TMB) and clinical outcomes. Our findings underscore the complexity of OSA biology and provide a foundation for developing personalized treatment strategies targeting tumor heterogeneity and immune interactions. |
| format | Article |
| id | doaj-art-df6cc060ca97480d99adf93a1995f6c6 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-df6cc060ca97480d99adf93a1995f6c62024-11-24T12:31:59ZengSpringerDiscover Oncology2730-60112024-11-0115111710.1007/s12672-024-01523-xIntegrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcomaDongan He0Xiaoqian Che1Haiming Zhang2Jiandong Guo3Lei Cai4Jian Li5Jinxi Zhang6Xin Jin7Jianfeng Wang8Department of Orthopaedics, Hangzhou Ninth People’s HospitalDepartment of Orthopaedics, Hangzhou Ninth People’s HospitalDepartment of Orthopaedics, Hangzhou Ninth People’s HospitalDepartment of Orthopaedics, Hangzhou Ninth People’s HospitalDepartment of Orthopaedics, Hangzhou Ninth People’s HospitalDepartment of Orthopaedics, Hangzhou Ninth People’s HospitalDepartment of Orthopaedics, Hangzhou Ninth People’s HospitalDepartment of Orthopaedics, Hangzhou Ninth People’s HospitalDepartment of Orthopaedics, Hangzhou Ninth People’s HospitalAbstract Osteosarcoma (OSA) is a primary bone malignancy characterized by its aggressive nature and high propensity for metastasis. Despite advancements in multimodal therapies, the clinical outcomes for OSA patients remain suboptimal, necessitating deeper molecular insights for improved therapeutic strategies. Here, we employed single-cell RNA sequencing (scRNA-seq) to elucidate the cellular heterogeneity and transcriptional dynamics of OSA tumors. Our study identified eleven distinct tumor cell subpopulations, including osteoblastic, chondroblastic, and myeloid lineages, each exhibiting unique transcriptional profiles associated with disease progression and metastasis. Epithelial-mesenchymal transition (EMT) emerged as a critical process driving aggressive phenotypes, supported by gene set enrichment analyses (GSVA) and transcription factor regulatory network analyses. Integration of copy number variation (CNV) data highlighted genomic alterations in osteoblastic and chondroblastic cells, implicating potential therapeutic targets. Furthermore, immune cell infiltration analyses revealed distinct immune profiles across OSA subtypes, correlating with tumor mutational burden (TMB) and clinical outcomes. Our findings underscore the complexity of OSA biology and provide a foundation for developing personalized treatment strategies targeting tumor heterogeneity and immune interactions.https://doi.org/10.1007/s12672-024-01523-xOsteosarcomaSingle-cell analysisHeterogeneityEpithelial–mesenchymal transitionPersonalized medicine |
| spellingShingle | Dongan He Xiaoqian Che Haiming Zhang Jiandong Guo Lei Cai Jian Li Jinxi Zhang Xin Jin Jianfeng Wang Integrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma Discover Oncology Osteosarcoma Single-cell analysis Heterogeneity Epithelial–mesenchymal transition Personalized medicine |
| title | Integrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma |
| title_full | Integrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma |
| title_fullStr | Integrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma |
| title_full_unstemmed | Integrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma |
| title_short | Integrated single-cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma |
| title_sort | integrated single cell analysis reveals heterogeneity and therapeutic insights in osteosarcoma |
| topic | Osteosarcoma Single-cell analysis Heterogeneity Epithelial–mesenchymal transition Personalized medicine |
| url | https://doi.org/10.1007/s12672-024-01523-x |
| work_keys_str_mv | AT donganhe integratedsinglecellanalysisrevealsheterogeneityandtherapeuticinsightsinosteosarcoma AT xiaoqianche integratedsinglecellanalysisrevealsheterogeneityandtherapeuticinsightsinosteosarcoma AT haimingzhang integratedsinglecellanalysisrevealsheterogeneityandtherapeuticinsightsinosteosarcoma AT jiandongguo integratedsinglecellanalysisrevealsheterogeneityandtherapeuticinsightsinosteosarcoma AT leicai integratedsinglecellanalysisrevealsheterogeneityandtherapeuticinsightsinosteosarcoma AT jianli integratedsinglecellanalysisrevealsheterogeneityandtherapeuticinsightsinosteosarcoma AT jinxizhang integratedsinglecellanalysisrevealsheterogeneityandtherapeuticinsightsinosteosarcoma AT xinjin integratedsinglecellanalysisrevealsheterogeneityandtherapeuticinsightsinosteosarcoma AT jianfengwang integratedsinglecellanalysisrevealsheterogeneityandtherapeuticinsightsinosteosarcoma |