Objective To investigate the expression and prognostic value of FOXO1 gene in liver cancer tissues based on TCGA and HPA databases.

Methods The RNA-seq data of FOXO1 gene in liver cancer were downloaded from TCGA. The difference of FOXO1 gene expression between tumor and adjacent tissues was obtained via R software. The correlation between FOXO1 and clinicopathological features of liver cancer patients was analyzed. Survival analysis was carried out to evaluate the prognostic significance of FOXO1 gene expression in liver cancer patients. Univariate and multivariate Cox analyses were performed to explore prognostic factors. The correlation between FOXO1 expression and TIICs in tumor microenvironment was performed by CIBERSORT. KEGG pathways enrichment analysis was performed for the potential function of FOXO1 gene in liver cancer.

Results FOXO1 was downregulated in liver cancer tissues compared with normal tissues (P=1.321E-15). Survival analysis showed that high expression of FOXO1 was positively associated with favorable OS of liver cancer patients (P < 0.05). Clinical stage, T and M stages could be prognostic indicators while FOXO1 wasn't an independent prognostic factor in patients with liver cancer. In TME of liver cancer, the expression of FOXO1 was positively correlated with resting memory CD4 T cells and naive B cells while negatively related to activated memory CD4 T cells and macrophages M2. GSEA identified that FOXO1 participated in multiple cancer-related pathways.

Conclusion FOXO1 is down-regulated in liver cancer tissues, and its expression level is associated with OS of patients. FOXO1 might be a biomarker related to the prognosis of liver cancer patients and is expected to be a target for diagnosis and treatment of liver cancer.