The prognostic significance of FoxM1 and its immune regulatory function in Liver Hepatocellular Carcinoma

Abstract

Abstract Liver hepatocellular carcinoma (LIHC) is one of the most common malignant tumors in the world with a poor prognosis. FoxM1, a known transcription factor, plays a principal role in the progression and development of multiple tumors. However, the relationships between FoxM1 expression, tumor immunity, and prognosis in LIHC remain unclear. Here we investigated the expression of FoxM1, its prognostic value and immune cell infiltration in LIHC via Oncomine, TIMER, GEPIA, HCCDB and Kaplan-Meier plotter databases. FoxM1 expression was significantly higher in LIHC and correlated with tumor stage, grade, and TP53 mutation status. The high expression of FoxM1 was related to the poor prognosis of LIHC patients, which was influenced by the abundance of immune infiltrates including B cells, CD4+T cells, CD8+T cells and Tregs. FoxM1 showed strong correlations with the infiltrating levels of different immune cell subtypes including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. FoxM1 expression was also significantly positively correlated with the expression of immune checkpoint molecules such as PD-1, CTLA-4, LAG3 and HAVCR2. What’s more, we found that inhibition of FoxM1 enhanced T-cell-mediated cytotoxicity against liver cancer cells via modulating PD-L1 expression. In conclusion, our results demonstrated that FoxM1 could be a potential prognostic target involved in its immune regulatory function in LIHC.