Abstract
Background: Forkhead box P (FOXP) family was introduced as a double-edged sword in tumorigenesis and influenced immunotherapy response by modulating host immunity. This study aimed to summarize the involvement of the FOXP family in non-small cell lung cancer (NSCLC). Methods: The UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA), and Reverse transcription-quantitative polymerase chain reaction (RT‒qPCR) were used to analyse the expression levels of the FOXP family in NSCLC. The prognostic impact was evaluated using Kaplan-Meier Plotter. MethSurv, UALCAN, and cBioPortal were applied to analyse the DNA methylation and mutation status of the FOXP family respectively. COEXPEDIA, STRING, and GeneMANIA were used to explore the interaction mechanism. Finally, TISIDB was used to investigate all of the immune-related characteristics regulated by the FOXP family. Results: The expression levels of FOXP1/3/4 were dysregulated in NSCLC tissues than that in normal tissues. Groups with low expression levels of FOXP1/4 and high expression levels of FOXP2/3 were associated with poor prognosis in NSCLC. The transcriptional levels of FOXP2/3/4 were correlated with DNA methylation in NSCLC. FOXP1/3/4 DNA methylation were correlated with prognosis. Pathway enrichment analysis indicated the FOXP family was mainly related to immune-related pathways. After DNA methylation, the correlations between FOXP family and immune factors were opposite to that before alteration in NSCLC. Conclusion: This study elucidated FOXP family could serve as vital diagnostic and prognostic biomarkers in NSCLC. Our study highlighted novel potential functions of FOXP family DNA methylation in regulation of immune-related signatures in NSCLC.