Department of Orthopedics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
Department of Orthopedics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
J Appl Genet. 2024 Feb;65(1):121-136. doi: 10.1007/s13353-023-00805-4. Epub 2023 Nov 25.
Sarcoma is a malignant tumor originating from mesenchymal tissue with a poor prognosis. Atypical chemokine receptor 1 (ACKR1) is found closely related to cancer progression. However, the effects of ACKR1 in soft tissue sarcoma have not been well investigated. Therefore, our present study is devoted to analyze the functions of ACKR1 in sarcoma progression and its potential mechanism. We detected the expression of ACKR1 in the Cancer Genome Atlas (TCGA)-pan-cancer database, TCGA-Sarcoma from TCGA databases, and GSE21122 from Gene Expression Omnibus (GEO) database. The relationships between ACKR1 expression, clinicopathological data, and survival status were evaluated in the TCGA-Sarcoma database. Moreover, overexpression negative control (OE-NC) and overexpression ACKR1 (OE-ACKR1) were used to further verify the effects of ACKR1 overexpression in the progression of sarcoma cells by using Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR), cell counting kit-8 (CCK-8), 5-Ethyny-2'-Deoxyuridine (EdU), wound healing, transwell assay, and flow cytometry assays. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analyses were carried out to explore the potential enriched biological process of ACKR1 expression in sarcoma. Furthermore, tumor-immune system interactions databases (TISIDB) were applied to further confirm the relations between ACKR1 and tumor immune microenvironment in sarcoma. Our study found that ACKR1 is downregulated in multiple cancers (including sarcoma), and low expression of ACKR1 is related to poor survival status in sarcoma. The biological experiments found that promoting expression of ACKR1 can suppress sarcoma cell proliferation, migration, invasion, promote cell apoptosis, and arrest cell cycle. The GO-KEGG, GSEA, and TISIDB analysis showed that ACKR1 is related to the tumor immune microenvironment. In conclusion, low expression of ACKR1 presented as an independent prognostic biomarker in sarcoma. Overexpression of ACKR1 can significantly suppress cell progression ability in sarcoma by regulating the immune microenvironment.
肉瘤是一种起源于间叶组织的恶性肿瘤，预后较差。非典型趋化因子受体 1（ACKR1）与癌症的进展密切相关。然而，ACKR1 在软组织肉瘤中的作用尚未得到很好的研究。因此，本研究旨在分析 ACKR1 在肉瘤进展中的功能及其潜在机制。我们在癌症基因组图谱（TCGA）-泛癌数据库、TCGA-Sarcoma 数据库和基因表达综合数据库（GEO）的 GSE21122 数据库中检测了 ACKR1 的表达。在 TCGA-Sarcoma 数据库中评估了 ACKR1 表达与临床病理数据和生存状态之间的关系。此外，我们使用逆转录-定量聚合酶链反应（RT-qPCR）、细胞计数试剂盒-8（CCK-8）、5-乙炔基-2'-脱氧尿苷（EdU）、划痕愈合、Transwell 检测和流式细胞术检测来进一步验证 ACKR1 过表达对肉瘤细胞进展的影响。我们进行了基因本体论（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）分析，以探讨 ACKR1 在肉瘤中表达的潜在富集生物学过程。此外，我们应用肿瘤-免疫系统相互作用数据库（TISIDB）进一步证实了 ACKR1 与肉瘤肿瘤免疫微环境之间的关系。我们的研究发现，ACKR1 在多种癌症（包括肉瘤）中下调，ACKR1 低表达与肉瘤患者的不良生存状态有关。生物学实验发现，促进 ACKR1 的表达可以抑制肉瘤细胞的增殖、迁移和侵袭，促进细胞凋亡，阻滞细胞周期。GO-KEGG、GSEA 和 TISIDB 分析表明，ACKR1 与肿瘤免疫微环境有关。综上所述，ACKR1 的低表达在肉瘤中作为一个独立的预后生物标志物。ACKR1 的过表达通过调节免疫微环境，显著抑制肉瘤细胞的进展能力。
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