Xiao-yu He , Liu-yi Que , Fan Yang , Yi Feng , Dong Ren , Xiang Song
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The nine cell types were identified, including fibroblasts, myeloid cells, osteoblasts, TILs, osteoclasts, proliferative osteoblasts, pericytes, endothelial cells, and B cells. Post-chemotherapy treatment, the proportions of myeloid cells and TILs in OS were declined, while the number of osteoblasts was elevated. Besides, a decrease was observed in CD74, FTL, FTH1, MT1X and MT2A, and an increase in PTN, COL3A1, COL1A1, IGFBP7 and FN1. Meanwhile, EMT, DNA repair, G2M checkpoint, and E2F targets were highly enriched post-chemotherapy. Furthermore, there was a down-regulation in the proportions of CD14 monocytes, Tregs, NK cells and CD1C-/CD141-DCs, while an up-regulation was observed in the proportions of SELENOP macrophages, IL7R macrophages, COL1A1 macrophages, CD1C DCs, CD4+ T cells and CD8+ T cells. Overall, these findings revealed changes in the tumor microenvironment of OS post-chemotherapy treatment, providing a new direction for investigating OS treatment.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"46 ","pages":"Article 100604"},"PeriodicalIF":3.4000,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000848/pdfft?md5=435ec41b8170ff8ca7ceda4cccbac000&pid=1-s2.0-S2212137424000848-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Single-cell transcriptional profiling in osteosarcoma and the effect of neoadjuvant chemotherapy on the tumor microenvironment\",\"authors\":\"Xiao-yu He , Liu-yi Que , Fan Yang , Yi Feng , Dong Ren , Xiang Song\",\"doi\":\"10.1016/j.jbo.2024.100604\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Osteosarcoma (OS), a malignant tumor, originates from the bone marrow. Currently, treatment for OS remains limited, making it urgent to understand the immune response in the tumor microenvironment of patients with OS. A comprehensive bioinformatics analysis was performed, including cell clustering subgroups, differential expression genes screening, proposed temporal order, and genomic variant analysis on single-cell RNA-sequencing data, from ten pre-chemotherapy patients and eleven post-chemotherapy patients. Subsequently, we analyzed the differentiation trajectories of osteoblasts, osteoclasts, fibroblasts, myeloid cells, and tumor-infiltrating lymphocytes (TILs) in detail to compare the changes in cell proportions and differential genes pre- and post-chemotherapy. The nine cell types were identified, including fibroblasts, myeloid cells, osteoblasts, TILs, osteoclasts, proliferative osteoblasts, pericytes, endothelial cells, and B cells. Post-chemotherapy treatment, the proportions of myeloid cells and TILs in OS were declined, while the number of osteoblasts was elevated. Besides, a decrease was observed in CD74, FTL, FTH1, MT1X and MT2A, and an increase in PTN, COL3A1, COL1A1, IGFBP7 and FN1. Meanwhile, EMT, DNA repair, G2M checkpoint, and E2F targets were highly enriched post-chemotherapy. Furthermore, there was a down-regulation in the proportions of CD14 monocytes, Tregs, NK cells and CD1C-/CD141-DCs, while an up-regulation was observed in the proportions of SELENOP macrophages, IL7R macrophages, COL1A1 macrophages, CD1C DCs, CD4+ T cells and CD8+ T cells. 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引用次数: 0
摘要
骨肉瘤(Osteosarcoma,OS)是一种起源于骨髓的恶性肿瘤。目前,对骨肉瘤的治疗仍然有限,因此迫切需要了解骨肉瘤患者肿瘤微环境中的免疫反应。我们对10名化疗前患者和11名化疗后患者的单细胞RNA测序数据进行了全面的生物信息学分析,包括细胞聚类分组、差异表达基因筛选、拟时序和基因组变异分析。随后,我们详细分析了成骨细胞、破骨细胞、成纤维细胞、髓样细胞和肿瘤浸润淋巴细胞(TILs)的分化轨迹,比较了化疗前后细胞比例和差异基因的变化。研究确定了九种细胞类型,包括成纤维细胞、髓样细胞、成骨细胞、TILs、破骨细胞、增殖性成骨细胞、周细胞、内皮细胞和B细胞。化疗后,OS 中髓样细胞和 TIL 的比例下降,而破骨细胞的数量上升。此外,CD74、FTL、FTH1、MT1X和MT2A的含量下降,而PTN、COL3A1、COL1A1、IGFBP7和FN1的含量上升。同时,化疗后EMT、DNA修复、G2M检查点和E2F靶点高度富集。此外,CD14单核细胞、Tregs、NK细胞和CD1C-/CD141-DC的比例出现了下调,而SELENOP巨噬细胞、IL7R巨噬细胞、COL1A1巨噬细胞、CD1C DCs、CD4+ T细胞和CD8+ T细胞的比例则出现了上调。总之,这些发现揭示了化疗后OS肿瘤微环境的变化,为研究OS的治疗提供了新的方向。
Single-cell transcriptional profiling in osteosarcoma and the effect of neoadjuvant chemotherapy on the tumor microenvironment
Osteosarcoma (OS), a malignant tumor, originates from the bone marrow. Currently, treatment for OS remains limited, making it urgent to understand the immune response in the tumor microenvironment of patients with OS. A comprehensive bioinformatics analysis was performed, including cell clustering subgroups, differential expression genes screening, proposed temporal order, and genomic variant analysis on single-cell RNA-sequencing data, from ten pre-chemotherapy patients and eleven post-chemotherapy patients. Subsequently, we analyzed the differentiation trajectories of osteoblasts, osteoclasts, fibroblasts, myeloid cells, and tumor-infiltrating lymphocytes (TILs) in detail to compare the changes in cell proportions and differential genes pre- and post-chemotherapy. The nine cell types were identified, including fibroblasts, myeloid cells, osteoblasts, TILs, osteoclasts, proliferative osteoblasts, pericytes, endothelial cells, and B cells. Post-chemotherapy treatment, the proportions of myeloid cells and TILs in OS were declined, while the number of osteoblasts was elevated. Besides, a decrease was observed in CD74, FTL, FTH1, MT1X and MT2A, and an increase in PTN, COL3A1, COL1A1, IGFBP7 and FN1. Meanwhile, EMT, DNA repair, G2M checkpoint, and E2F targets were highly enriched post-chemotherapy. Furthermore, there was a down-regulation in the proportions of CD14 monocytes, Tregs, NK cells and CD1C-/CD141-DCs, while an up-regulation was observed in the proportions of SELENOP macrophages, IL7R macrophages, COL1A1 macrophages, CD1C DCs, CD4+ T cells and CD8+ T cells. Overall, these findings revealed changes in the tumor microenvironment of OS post-chemotherapy treatment, providing a new direction for investigating OS treatment.
期刊介绍:
The Journal of Bone Oncology is a peer-reviewed international journal aimed at presenting basic, translational and clinical high-quality research related to bone and cancer.
As the first journal dedicated to cancer induced bone diseases, JBO welcomes original research articles, review articles, editorials and opinion pieces. Case reports will only be considered in exceptional circumstances and only when accompanied by a comprehensive review of the subject.
The areas covered by the journal include:
Bone metastases (pathophysiology, epidemiology, diagnostics, clinical features, prevention, treatment)
Preclinical models of metastasis
Bone microenvironment in cancer (stem cell, bone cell and cancer interactions)
Bone targeted therapy (pharmacology, therapeutic targets, drug development, clinical trials, side-effects, outcome research, health economics)
Cancer treatment induced bone loss (epidemiology, pathophysiology, prevention and management)
Bone imaging (clinical and animal, skeletal interventional radiology)
Bone biomarkers (clinical and translational applications)
Radiotherapy and radio-isotopes
Skeletal complications
Bone pain (mechanisms and management)
Orthopaedic cancer surgery
Primary bone tumours
Clinical guidelines
Multidisciplinary care
Keywords: bisphosphonate, bone, breast cancer, cancer, CTIBL, denosumab, metastasis, myeloma, osteoblast, osteoclast, osteooncology, osteo-oncology, prostate cancer, skeleton, tumour.