Single-cell RNA-seq reveals intratumoral heterogeneity in osteosarcoma patients: A review

Thomas, Dylan D.; Lacinski, Ryan A.; Lindsey, Brock A.

doi:10.1016/j.jbo.2023.100475

Cited by 9 publications

(6 citation statements)

References 100 publications

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“…Furthermore, single-cell RNA sequencing (scRNA-seq) analysis, potentially employing a targeted approach, could elucidate the expression of FGF23 in distinct subsets of UPSb that have also been previously identified by Yuan et al [30]. In parallel, the search for FGF23 expression in the complex osteosarcoma microenvironment, which has been recently highlighted by scRNA-seq investigations, could help with understanding if FGF23 is not expressed in any OS and associated normal subpopulation [31][32][33]. Indeed, OS heterogeneity in terms of subtypes, cells of origin [34], and tumour complexity might require further evaluation.…”

Section: Discussionmentioning

confidence: 83%

FGF23 Expression Is a Promising Immunohistochemical Diagnostic Marker for Undifferentiated Pleomorphic Sarcoma of Bone (UPSb)

Al-Hassi,

Ali,

Cooke

et al. 2024

Genes

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Background: Undifferentiated pleomorphic sarcoma of bone (UPSb) is a rare primary bone sarcoma that lacks a specific line of differentiation. Distinguishing between UPSb and other malignant bone sarcomas, including dedifferentiated chondrosarcoma and osteosarcoma, is challenging due to their overlapping features. We have previously identified that UPSb tumours have elevated mRNA levels of Fibroblast Growth Factor 23 (FGF23) transcripts compared to other sarcomas including osteosarcoma. In the present study, we evaluated the specificity and practicality of FGF23 immunoreactivity as a specific diagnostic tool to differentiate UPSb tumours from osteosarcomas and dedifferentiated chondrosarcomas. Methods: A total of 10 UPSb, 10 osteosarcoma, and 10 dedifferentiated chondrosarcoma cases (all high-grade), were retrieved and immunohistochemistry for FGF23 was performed. Results: FGF23 protein was expressed at high levels in 80–90% of undifferentiated pleomorphic sarcoma of the bone cases, whereas it was expressed at significantly lower levels in dedifferentiated chondrosarcoma and osteosarcoma cases. A semiquantitative analysis, considering the intensity of immunoreactivity, confirmed significantly elevated FGF23 expression levels in UPSb tissues compared to those observed in osteosarcoma and dedifferentiated chondrosarcoma tissues. Conclusions: The results we present here suggest that FGF23 immunohistochemistry may be a useful tool to aid in differentiating UPSb from morphologically similar malignant bone sarcomas, especially in situations where sampling is restricted and there is limited clinical information available.

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Section: Discussionmentioning

confidence: 83%

FGF23 Expression Is a Promising Immunohistochemical Diagnostic Marker for Undifferentiated Pleomorphic Sarcoma of Bone (UPSb)

Al-Hassi,

Ali,

Cooke

et al. 2024

Genes

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“…It is known to be effective against various types of cancer such as liver cancer, colorectal cancer, and lung cancer [21][22][23] . Recently, the effectiveness of matrine against OS has been substantiated through experimentation [24] . Our experiment primarily involves utilizing single-cell sequencing for comprehensive investigation and genomic-level analysis.…”

Section: Resultsmentioning

confidence: 99%

“…This method is instrumental in highlighting tumor heterogeneity, thus playing a significant role in evaluating the treatment outcomes and survival prognoses of OS. Furthermore, singlecell sequencing significantly impacts network pharmacology [24] . It aids in precision targeting of drugs, evaluating drug efficacy, and providing a better understanding of the molecular mechanisms underlying drug action.…”

Section: Resultsmentioning

confidence: 99%

Deciphering Matrine's Therapeutic Mechanism in Osteosarcoma: Insights from Network Pharmacology and Single-Cell RNA Sequencing

Xie,

Ma,

et al. 2024

IJPS

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This study aimed to investigate the potential mechanisms underlying the therapeutic effect of matrine in osteosarcoma using network pharmacology and single-cell ribonucleic acid sequencing. Matrine's potential gene targets were sourced from multiple databases; comparative toxicogenomics database, SwissTargetPrediction, Binding DB, and TargetNet. We extracted gene expression data related to osteosarcoma from the GSE14359 dataset. To discern the activation pathways of genes linked to both the drug and disease, we performed differential gene analysis, Kyoto encyclopedia of genes and genomes pathway analysis, and gene ontology enrichment analysis. By employing both weighted gene co-expression network analysis and differential analysis, we pinpointed critical genes associated with osteosarcoma. Protein-protein interaction analysis was utilized to highlight hub genes. Furthermore, module analysis revealed key gene clusters that affect matrine. For a comprehensive evaluation of matrine's pharmacological targets and signaling pathways in osteosarcoma, single-cell ribonucleic acid sequencing was carried out on the GSE162454 dataset using the Seurat package in R. A total of 15 cell clusters were identified, and the analysis results suggested that the mechanism of matrine's action on osteosarcoma may involve macrophages. This study elucidated the targets and pathways through which matrine acts on osteosarcoma using network pharmacology. Moreover, single-cell sequencing identified macrophages as key cellular markers for matrine's action in osteosarcoma. These findings provide new therapeutic evidence for clinical treatment strategies.

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“…High level cell type annotations were established using unsupervised clustering results, gene set enrichment analysis, and manual annotation based on the literature for accepted human cell type markers 57 . Briefly, markers included CD3E for T cells, CTSK for osteoclasts, CD68 for macrophages, S100A12 for neutrophils, COL1A1/ALPL/FAP for tumor/fibroblasts, FLT3 for dendritic cells, MS4A1/JCHAIN for B cells, ESAM/PLVAP for endothelial cells, TOP2A for cycling cells, and GATA2/MS4A2 for mast cells.…”

Section: Methodsmentioning

confidence: 99%

Single-cell RNA sequencing reveals the cellular and molecular heterogeneity of treatment-naïve primary osteosarcoma in dogs

Ammons

Hopkins

Cronise

et al. 2023

Preprint

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Osteosarcoma (OS) is a heterogeneous, aggressive malignancy of the bone that disproportionally affects children and adolescents. Therapeutic interventions for OS are limited, which is in part due to the complex tumor microenvironment (TME) that has proven to be refractory to immunotherapies. Thus, there is a need to better define the complexity of the OS TME. To address this need, we used single-cell RNA sequencing (scRNA-seq) to describe the cellular and molecular composition of the TME in 6 treatment-naïve dogs with spontaneously occurring primary OS. Through analysis of 35,310 cells, we identified 30 distinct immune cell types, 9 unique tumor populations, 1 cluster of fibroblasts, and 1 cluster of endothelial cells. Independent reclustering of major cell types revealed the presence of follicular helper T cells, mature regulatory dendritic cells (mregDCs), and 8 transcriptomically distinct macrophage/monocyte populations. Cell-cell interaction inference analysis predicted that mregDCs and tumor-associated macrophages (TAMs) play key roles in modulating T cell mediate immunity. Furthermore, we used publicly available human OS scRNA-seq data to complete a cross-species cell type gene signature homology analysis. The analysis revealed a high degree of cell type gene signature homology between species, suggesting the cellular composition of OS is largely conserved between humans and dogs. Our findings provide key new insights into the biology of canine OS and highlight the conserved features of OS across species. Generally, the data presented here acts as a cellular and molecular roadmap of canine OS which can be applied to advance the translational immuno-oncology research field.

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Single-cell RNA-seq reveals intratumoral heterogeneity in osteosarcoma patients: A review

Cited by 9 publications

References 100 publications

FGF23 Expression Is a Promising Immunohistochemical Diagnostic Marker for Undifferentiated Pleomorphic Sarcoma of Bone (UPSb)

FGF23 Expression Is a Promising Immunohistochemical Diagnostic Marker for Undifferentiated Pleomorphic Sarcoma of Bone (UPSb)

Deciphering Matrine's Therapeutic Mechanism in Osteosarcoma: Insights from Network Pharmacology and Single-Cell RNA Sequencing

Single-cell RNA sequencing reveals the cellular and molecular heterogeneity of treatment-naïve primary osteosarcoma in dogs

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