SPP1和CSF1在肝细胞癌中的重要致癌和免疫功能。
Important oncogenic and immunogenic roles of SPP1 and CSF1 in hepatocellular carcinoma.
发表日期:2023 Apr 25
作者:
Tianxin Xiang, Na Cheng, Bo Huang, Xujun Zhang, Ping Zeng
来源:
GENES & DEVELOPMENT
摘要:
肝癌的治疗和预后仍然是医学研究的重点。研究表明,SPP1和CSF1在细胞增殖、侵袭和转移中扮演重要角色。因此,本研究分析了SPP1和CSF1在肝细胞癌(HCC)中的致癌和免疫学作用。我们发现HCC中SPP1和CSF1的表达水平明显增加且呈正相关。高SPP1表达与不良的OS、DSS、PFS和RFS显著相关,它不受性别、酒精使用、HBV或种族的影响,而CSF1受这些因素的影响。高表达的SPP1和CSF1表明免疫细胞浸润水平较高,并在R软件包ESTIMATE中具有较高的免疫评分。进一步的分析揭示了SPP1和CSF1之间的许多基因共同表达,这些基因主要涉及信号转导、膜的整合组分、蛋白结合和成骨细胞分化。此外,我们使用cytoHubba筛选出十个重要基因,其中四个基因的表达与HCC患者的预后显著相关。最后,我们通过体外实验证明了SPP1和CSF1的致癌和免疫学作用。减少SPP1或CSF1表达均可显著减少HCC细胞的增殖及CSF1、SPP1和其他四个重要基因的表达。该研究表明,SPP1和CSF1相互作用,并具有成为HCC治疗和预后靶点的潜力。©2023作者们。
The treatment and prognosis of liver cancer remain the focus of medical research. Studies have shown that SPP1 and CSF1 play important roles in cell proliferation, invasion, and metastasis. Therefore, this study analyzed the oncogenic and immunologic roles of SPP1 and CSF1 in hepatocellular carcinoma (HCC). We found that the expression levels of SPP1 and CSF1 in HCC were markedly increased and positively correlated. High SPP1 expression was significantly associated with poor OS, DSS, PFS, and RFS. It was not affected by gender, alcohol use, HBV, or race, whereas CSF1 was affected by these factors. Higher expression levels of SPP1 and CSF1 indicated higher levels of immune cell infiltration and a higher immune score with the R software package ESTIMATE. Further analysis revealed that many genes work co-expressed between SPP1 and CSF1 with the LinkedOmics database, which were mainly involved in signal transduction, the integral components of the membrane, protein binding, and osteoclast differentiation. In addition, we screened ten hub genes using cytoHubba, among which the expression of four genes was significantly associated with the prognosis of HCC patients. Finally, we demonstrated the oncogenic and immunologic roles of SPP1 and CSF1 using the vitro experiments. Reducing the expression of either SPP1 or CSF1 could significantly reduce the proliferation of HCC cells and the expression of CSF1, SPP1, and the other four hub genes. This study suggested that SPP1 and CSF1 interact with each other and have the potential to be therapeutic and prognostic targets for HCC.© 2023. The Author(s).