The forkhead box O (FOXO)
transcription factors (TFs) family are frequently mutated, deleted, or amplified in various human
cancers, making them attractive candidates for
therapy. However, their roles in pan-
cancer remain unclear. Here, we evaluated the expression, prognostic value, mutation, methylation, and clinical features of four FOXO family genes (FOXO1, FOXO3, FOXO4, and FOXO6) in 33 types of
cancers based on the
Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases. We used a single sample gene set enrichment analysis (ssGSEA) algorithm to establish a novel index called "FOXOs score". Moreover, we investigated the association between the FOXOs score and tumor microenvironment (TME), the responses to multiple treatments, along with drug resistance. We found that the FOXO family genes participated in
tumor progression and were related to the prognosis in various types of
cancer. We calculated the FOXOs score and found that it was significantly correlated with multiple malignant pathways in pan-
cancer, including Wnt/
beta-catenin signaling,
TGF-beta signaling, and hedgehog signaling. In addition, the FOXOs score was also associated with multiple immune-related characteristics. Furthermore, the FOXOs score was sensitive for predicting the efficacy of diverse treatments in multiple
cancers, especially
immunotherapy. In conclusion, FOXO family genes were vital in pan-
cancer and were strongly correlated with the TME. A high FOXOs score indicated an excellent immune-activated TME and sensitivity to multiple treatments. Hence, the FOXOs score might potentially be used as a
biomarker in patients with a
tumor.