Comprehensive Analysis of FOXO1 as a Tumour Suppressor Biomarker Related to Immune Infiltration and Cell Proliferation of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality, and effective biomarkers for indicating prognosis and treatment have still not been fully investigated. Forkhead box O1 (FOXO1), as a crucial transcription factor, its role remains to be elucidated in HCC. Herein, by combining bioinformatics techniques and basic experiments, the expression and function of FOXO1 in HCC were preliminarily explored. The expression profile, prognostic analysis, mutation landscape, immune infiltration abundance and tumour stemness index of FOXO1 were determined in TCGA and GEO databases. Moreover, a FOXO1-related nomogram was constructed and validated in the HCC cohort. Ultimately, the expression and function of FOXO1 in HCC were verified through basic experiments, such as western blotting, RT-qPCR, immunohistochemical analysis, CCK8 assay and clone formation assay. The expression of FOXO1 was decreased and was associated with a favourable prognosis in majority of cancers. Mutation landscapes of FOXO1 in various cancers were described and revealed the significant association between FOXO1 expression and TMB/MSI. A FOXO1-based Nomogram was constructed and verified in HCC cohort. The expression and function of FOXO1 were closely related to the HCC immune microenvironment. Moreover, there was a negative correlation between the FOXO1 expression and tumour stemness index. Finally, the expression pattern of FOXO1 in HCC and its association with tumour proliferation ability were verified through basic experiments. FOXO1 was identified to regulate the immune microenvironment and the tumour proliferation ability in HCC, demonstrating its potential as a therapeutic target for HCC.