PDF(Pubmed)
Abstract：
Tumour-associated macrophages (TAMs), encompassing M1 and M2 subtypes, exert significant effects on osteosarcoma (OS) progression and immunosuppression. However, the impacts of TAM-derived biomarkers on the progression of OS remains limited. The GSE162454 profile was subjected to single-cell RNA (scRNA) sequencing analysis to identify crucial mediators between TAMs and OS cells. The clinical features, effects and mechanisms of these mediators on OS cells and tumour microenvironment were evaluated via biological function experiments and molecular biology experiments. Phosphodiesterase 4C (PDE4C) was identified as a pivotal mediator in the communication between M2 macrophages and OS cells. Elevated levels of PDE4C were detected in OS tissues, concomitant with M2 macrophage level, unfavourable prognosis and metastasis. The expression of PDE4C was observed to increase during the conversion process of THP-1 cells to M2 macrophages, which transferred the PDE4C mRNA to OS cells through exosome approach. PDE4C increased OS cell proliferation and mobility via upregulating the expression of collagens. Furthermore, a positive correlation was observed between elevated levels of PDE4C and increased TIDE score, decreased response rate following immune checkpoint therapy, reduced TMB and diminished PDL1 expression. Collectively, PDE4C derived from M2 macrophages has the potential to enhance the proliferation and mobility of OS cells by augmenting collagen expression. PDE4C may serve as a valuable biomarker for prognosticating patient outcomes and response rates following immunotherapy.
摘要：
肿瘤相关巨噬细胞（TAMs），包括M1和M2亚型，对骨肉瘤（OS）的进展和免疫抑制有显著影响。然而,TAM衍生的生物标志物对OS进展的影响仍然有限.对GSE162454谱进行单细胞RNA(scRNA)测序分析以鉴定TAM和OS细胞之间的关键介质。临床特征，通过生物学功能实验和分子生物学实验评估了这些介质对OS细胞和肿瘤微环境的影响和机制。磷酸二酯酶4C（PDE4C）被认为是M2巨噬细胞和OS细胞之间通讯的关键介质。在OS组织中检测到PDE4C水平升高，伴随着M2巨噬细胞水平，预后不良和转移。在THP-1细胞向M2型巨噬细胞转化过程中,观察到PDE4C的表达增加,通过外泌体方法将PDE4CmRNA转移至OS细胞。PDE4C通过上调胶原蛋白的表达增加OS细胞的增殖和移动性。此外，PDE4C水平升高与TIDE评分升高呈正相关，免疫检查点治疗后反应率降低，减少TMB和减少PDL1表达。总的来说，源自M2巨噬细胞的PDE4C具有通过增强胶原表达来增强OS细胞的增殖和移动性的潜力。PDE4C可以作为预测患者预后和免疫疗法后反应率的有价值的生物标志物。
