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单细胞 RNA 测序揭示骨巨细胞瘤和骨肉瘤中 EGFL7 和 VEGF 的差异表达。

Single-cell RNA sequencing reveals differential expression of EGFL7 and VEGF in giant-cell tumor of bone and osteosarcoma.

机构信息

School of Biomedical Sciences, University of Western Australia, Perth, WA 6009, Australia.

Department of Orthopaedics, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

出版信息

Exp Biol Med (Maywood). 2022 Jul;247(14):1214-1227. doi: 10.1177/15353702221088238. Epub 2022 Jun 13.

Abstract

is associated with tumor development and is accompanied by altered expression of pro-angiogenic factors. 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 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 in GCTB and OS and compare with that of and 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, in GCTB was expressed at highest levels in the endothelial cell (EC) cluster followed by osteoblasts, myeloid cells, and chondrocytes, respectively. In OS, exhibited highest expression in EC cell cluster followed by osteoblastic OS cells, myeloid cells 1, and carcinoma associated fibroblasts (CAFs), respectively. In comparison, - is expressed at highest levels in myeloid cells followed by OCs in GCTB, and in myeloid cells, and OCs in OS. - is expressed at highest levels in chondrocytes in GCTB and in OCs in OS. - is strongly enriched in ECs and is expressed at weak levels in all cell types in both GCTB and OS. (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

与肿瘤的发生发展有关,并伴有促血管生成因子表达的改变。 是一种新发现的抗原性因子,在乳腺癌、肺癌和急性髓系白血病等多种癌症中发挥作用。我们最近发现 在骨微环境中表达,但它在巨细胞瘤(GCTB)和骨肉瘤(OS)中的作用尚不清楚。本研究旨在通过单细胞 RNA 测序数据,检测 GCTB 和 OS 中 的基因表达谱,并与 和 的基因表达谱进行比较。采用深度差异表达分析方法,对其在 GCTB 和 OS 组成细胞类型中的表达进行了特征描述。值得注意的是,GCTB 中 的表达水平最高,分别存在于内皮细胞(EC)簇、成骨细胞、髓细胞和软骨细胞中。在 OS 中, 的表达水平最高,分别存在于 EC 细胞簇、成骨样 OS 细胞、髓细胞 1 和癌相关成纤维细胞(CAFs)中。相比之下,GCTB 中 的表达水平最高,存在于髓细胞中,其次是 OC,而在 OS 中, 的表达水平最高,存在于髓细胞和 OC 中。-在 GCTB 中表达水平最高的是软骨细胞,而在 OS 中则是 OC。-在 GCTB 和 OS 中,均强烈富集于 EC 中,而在所有细胞类型中表达水平均较弱。(或 RANKL)在 OS 中的 CAFs 和成骨样 OS 细胞中表达水平较高,而在 GCTB 中则表达于成骨细胞。本研究探讨了 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具有细胞类型特异性,可为 GCTB 和 OS 提供潜在的预后生物标志物和细胞类型靶向治疗。

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