The Pan-Cancer Multi-Omics Landscape of FOXO Family Relevant to Clinical Outcome and Drug Resistance

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Forkhead box O (FOXO) transcription factors are frequently altered in human cancers.
• Their comprehensive roles across diverse cancer types remain largely undefined.
• FOXO family genes (FOXO1, FOXO3, FOXO4, FOXO6) are potential therapeutic targets.

Purpose of the Study:

• To investigate the expression, prognostic significance, and clinical relevance of FOXO family genes in pan-cancer.
• To develop and validate a novel index, the "FOXO s score", for assessing FOXO activity.
• To explore the association of the FOXOs score with the tumor microenvironment (TME), treatment responses, and drug resistance.

Main Methods:

• Utilized The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases for analysis across 33 cancer types.
• Employed a single sample gene set enrichment analysis (ssGSEA) algorithm to compute the FOXOs score.
• Correlated the FOXOs score with malignant pathways, immune characteristics, and treatment outcomes.

Main Results:

• FOXO family genes are implicated in tumor progression and exhibit prognostic value across various cancers.
• The FOXOs score significantly correlates with key oncogenic signaling pathways (Wnt/beta-catenin, TGF-beta, hedgehog).
• The FOXOs score is associated with immune-related features and predicts sensitivity to diverse treatments, particularly immunotherapy.

Conclusions:

• FOXO family genes play a vital role in pan-cancer biology and are closely linked to the TME.
• A high FOXOs score signifies an immune-activated TME and predicts favorable responses to therapies.
• The FOXOs score shows potential as a predictive biomarker for patient stratification and treatment selection in oncology.