Important oncogenic and immunogenic roles of SPP1 and CSF1 in hepatocellular carcinoma

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.