Sex differences in expression of immune elements emerge in children, young adults and mice with osteosarcoma
Abstract Background Males < 40 years old are more likely to be diagnosed with and die from osteosarcoma (OS). The underlying mechanisms may depend on sex differences in immune response. Methods We used SEER data to estimate survival differences between males and females aged < 40 years at OS d...
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Biology of Sex Differences |
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| Online Access: | https://doi.org/10.1186/s13293-020-00347-y |
| _version_ | 1818382747345879040 |
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| author | Lauren J. Mills Logan G. Spector David A. Largaespada Lindsay A. Williams |
| author_facet | Lauren J. Mills Logan G. Spector David A. Largaespada Lindsay A. Williams |
| author_sort | Lauren J. Mills |
| collection | DOAJ |
| description | Abstract Background Males < 40 years old are more likely to be diagnosed with and die from osteosarcoma (OS). The underlying mechanisms may depend on sex differences in immune response. Methods We used SEER data to estimate survival differences between males and females aged < 40 years at OS diagnosis. In NCI TARGET-OS cases, we determined sex differences in gene expression, conducted Gene Set Enrichment Analysis (GSEA), and applied the LM22 signature to identify biologic sex differences. We compared sex differences in gene expression profiles in TARGET-OS to those observed in Sleeping Beauty (SB) transposon mutagenesis accelerated Trp53 R270H -mutant mouse-OS and healthy adult osteoblasts. Results Males had worse 17-year overall survival than females (SEER p < 0.0001). From 87 TARGET-OS cases, we observed 1018 genes and 69 pathways that differed significantly by sex (adjusted p < 0.05). Pathway and gene lists overlapped with those from mice (p = 0.03) and healthy osteoblasts (p = 0.017), respectively. Pathways that differed significantly by sex were largely immune-based and included the PD-1/PD-L1 immunotherapy pathway. We observed sex differences in M2 macrophages (LM22; p = 0.056) and M1-M2 macrophage transition (GSEA; p = 0.037) in TARGET-OS. LM22 trends were similar in mice. Twenty-four genes differentially expressed by sex in TARGET-OS had existing cancer therapies. Conclusions Sex differences in OS gene expression were similar across species and centered on immune pathways. Identified sex-specific therapeutic targets may improve outcomes in young individuals with OS. |
| first_indexed | 2024-12-14T02:55:23Z |
| format | Article |
| id | doaj.art-1633e651a207489897de715e81af6df7 |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-12-14T02:55:23Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-1633e651a207489897de715e81af6df72022-12-21T23:19:38ZengBMCBiology of Sex Differences2042-64102021-01-0112111210.1186/s13293-020-00347-ySex differences in expression of immune elements emerge in children, young adults and mice with osteosarcomaLauren J. Mills0Logan G. Spector1David A. Largaespada2Lindsay A. Williams3Department of Pediatrics, University of Minnesota School of MedicineDepartment of Pediatrics, University of Minnesota School of MedicineDepartment of Pediatrics, University of Minnesota School of MedicineDepartment of Pediatrics, University of Minnesota School of MedicineAbstract Background Males < 40 years old are more likely to be diagnosed with and die from osteosarcoma (OS). The underlying mechanisms may depend on sex differences in immune response. Methods We used SEER data to estimate survival differences between males and females aged < 40 years at OS diagnosis. In NCI TARGET-OS cases, we determined sex differences in gene expression, conducted Gene Set Enrichment Analysis (GSEA), and applied the LM22 signature to identify biologic sex differences. We compared sex differences in gene expression profiles in TARGET-OS to those observed in Sleeping Beauty (SB) transposon mutagenesis accelerated Trp53 R270H -mutant mouse-OS and healthy adult osteoblasts. Results Males had worse 17-year overall survival than females (SEER p < 0.0001). From 87 TARGET-OS cases, we observed 1018 genes and 69 pathways that differed significantly by sex (adjusted p < 0.05). Pathway and gene lists overlapped with those from mice (p = 0.03) and healthy osteoblasts (p = 0.017), respectively. Pathways that differed significantly by sex were largely immune-based and included the PD-1/PD-L1 immunotherapy pathway. We observed sex differences in M2 macrophages (LM22; p = 0.056) and M1-M2 macrophage transition (GSEA; p = 0.037) in TARGET-OS. LM22 trends were similar in mice. Twenty-four genes differentially expressed by sex in TARGET-OS had existing cancer therapies. Conclusions Sex differences in OS gene expression were similar across species and centered on immune pathways. Identified sex-specific therapeutic targets may improve outcomes in young individuals with OS.https://doi.org/10.1186/s13293-020-00347-yOsteosarcomaSex differencesGene expressionSurvival disparitiesPediatric and young adult cancerMouse osteosarcoma |
| spellingShingle | Lauren J. Mills Logan G. Spector David A. Largaespada Lindsay A. Williams Sex differences in expression of immune elements emerge in children, young adults and mice with osteosarcoma Biology of Sex Differences Osteosarcoma Sex differences Gene expression Survival disparities Pediatric and young adult cancer Mouse osteosarcoma |
| title | Sex differences in expression of immune elements emerge in children, young adults and mice with osteosarcoma |
| title_full | Sex differences in expression of immune elements emerge in children, young adults and mice with osteosarcoma |
| title_fullStr | Sex differences in expression of immune elements emerge in children, young adults and mice with osteosarcoma |
| title_full_unstemmed | Sex differences in expression of immune elements emerge in children, young adults and mice with osteosarcoma |
| title_short | Sex differences in expression of immune elements emerge in children, young adults and mice with osteosarcoma |
| title_sort | sex differences in expression of immune elements emerge in children young adults and mice with osteosarcoma |
| topic | Osteosarcoma Sex differences Gene expression Survival disparities Pediatric and young adult cancer Mouse osteosarcoma |
| url | https://doi.org/10.1186/s13293-020-00347-y |
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