1.Bioinformatics Analysis on Key Genes and Immune Infiltration of Osteosarcoma.
Shuai LI ; Zhen-Zhong ZHENG ; Yu-Peng ZHANG ; Zi-Qun LIU ; Shi-Peng XIAO ; Zheng-Xiao OUYANG ; Bing WANG
Acta Academiae Medicinae Sinicae 2022;44(1):110-117
Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.
Bone Neoplasms/immunology*
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Computational Biology/methods*
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Gene Expression Profiling/methods*
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Humans
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Osteosarcoma/immunology*
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Phosphatidylinositol 3-Kinases/genetics*
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Tumor-Associated Macrophages/immunology*
2.2-Hexyl-4-Pentylenic Acid (HPTA) Stimulates the Radiotherapy-induced Abscopal Effect on Distal Tumor through Polarization of Tumor-associated Macrophages.
Wen Hua DUAN ; Li Ya JIN ; Zu Chao CAI ; David LIM ; Zhi Hui FENG
Biomedical and Environmental Sciences 2021;34(9):693-704
Objective:
The aim of this study was to explore the effects of 2-hexyl-4-pentylenic acid (HPTA) in combination with radiotherapy (RT) on distant unirradiated breast tumors.
Methods:
Using a rat model of chemical carcinogen (7,12-dimethylbenz[a]anthracene,DMBA)-induced breast cancer, tumor volume was monitored and treatment response was evaluated by performing HE staining, immunohistochemistry, immunofluorescence, qRT-PCR, and western blot analyses.
Results:
The results demonstrated that HPTA in combination with RT significantly delayed the growth of distant, unirradiated breast tumors. The mechanism of action included tumor-associated macrophage (TAM) infiltration into distant tumor tissues, M1 polarization, and inhibition of tumor angiogenesis by IFN-γ.
Conclusion
The results suggest that the combination of HPTA with RT has an abscopal effect on distant tumors
Animals
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Antineoplastic Agents/therapeutic use*
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Cell Proliferation/radiation effects*
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Combined Modality Therapy
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Cytokines/immunology*
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Fatty Acids, Unsaturated/therapeutic use*
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Female
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Mammary Neoplasms, Experimental/radiotherapy*
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Rats
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Tumor-Associated Macrophages/radiation effects*