关键词: EGFL7 Giant-cell tumor of bone VEGF differentially expressed genes osteosarcoma single cell sequencing

Mesh : Bone Neoplasms / genetics pathology Calcium-Binding Proteins / genetics EGF Family of Proteins / genetics metabolism Giant Cell Tumor of Bone / genetics metabolism pathology Humans Osteosarcoma / genetics Sequence Analysis, RNA Transcription Factors / metabolism Tumor Microenvironment / genetics Vascular Endothelial Growth Factor A / metabolism

来  源:   DOI:10.1177/15353702221088238

Abstract:
Dysregulation of angiogenesis is associated with tumor development and is accompanied by altered expression of pro-angiogenic factors. EGFL7 is a newly identified antigenic factor that plays a role in various cancers such as breast cancer, lung cancer, and acute myeloid leukemia. We have recently found that EGFL7 is expressed in the bone microenvironment, but its role in giant-cell tumor of bone (GCTB) and osteosarcoma (OS) is unknown. The aims of this study are to examine the gene expression profile of EGFL7 in GCTB and OS and compare with that of VEGF-A-D and TNFSF11 using single-cell RNA sequencing data. In-depth differential expression analyses were employed to characterize their expression in the constituent cell types of GCTB and OS. Notably, EGFL7 in GCTB was expressed at highest levels in the endothelial cell (EC) cluster followed by osteoblasts, myeloid cells, and chondrocytes, respectively. In OS, EGFL7 exhibited highest expression in EC cell cluster followed by osteoblastic OS cells, myeloid cells 1, and carcinoma associated fibroblasts (CAFs), respectively. In comparison, VEGF-A is expressed at highest levels in myeloid cells followed by OCs in GCTB, and in myeloid cells, and OCs in OS. VEGF-B is expressed at highest levels in chondrocytes in GCTB and in OCs in OS. VEGF-C is strongly enriched in ECs and VEGF-D is expressed at weak levels in all cell types in both GCTB and OS. TNFSF11 (or RANKL) shows high expression in CAFs and osteoblastic OS cells in OS, and osteoblasts in GCTB. This study investigates pro-angiogenic genes in GCTB and OS and suggests that these genes and their expression patterns are cell-type specific and could provide potential prognostic biomarkers and cell type target treatment for GCTB and OS.
摘要:
血管生成的失调与肿瘤的发展有关,并伴随着促血管生成因子表达的改变。EGFL7是一种新发现的抗原因子,在乳腺癌等各种癌症中发挥作用。肺癌,和急性髓细胞性白血病.我们最近发现EGFL7在骨骼微环境中表达,但其在骨巨细胞瘤(GCTB)和骨肉瘤(OS)中的作用尚不清楚。这项研究的目的是检查GCTB和OS中EGFL7的基因表达谱,并使用单细胞RNA测序数据与VEGF-A-D和TNFSF11进行比较。采用深入的差异表达分析来表征它们在GCTB和OS的组成细胞类型中的表达。值得注意的是,GCTB中的EGFL7在内皮细胞(EC)簇中表达最高,其次是成骨细胞,骨髓细胞,和软骨细胞,分别。在操作系统中,EGFL7在EC细胞群中表达最高,其次是成骨细胞OS细胞。骨髓细胞1和癌相关成纤维细胞(CAFs),分别。相比之下,VEGF-A在骨髓细胞中表达最高水平,其次是GCTB中的OCs,在骨髓细胞中,和OS中的OC。VEGF-B在GCTB中的软骨细胞和OS中的OC中以最高水平表达。VEGF-C在ECs中强烈富集,而VEGF-D在GCTB和OS中的所有细胞类型中以弱水平表达。TNFSF11(或RANKL)在OS中的CAFs和成骨细胞OS细胞中显示高表达,GCTB中的成骨细胞。这项研究调查了GCTB和OS中的促血管生成基因,并表明这些基因及其表达模式是细胞类型特异性的,可以为GCTB和OS提供潜在的预后生物标志物和细胞类型靶标治疗。
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