Exploring The Significance Of FOX Gene Family In Early Diagnosis And Treatment Of Tumors Based On Multi-omics Data

Objective: The forkhead box(FOX)protein family is a class of transcription factors with a winged helix structure in the DNA binding region.Previous studies have shown that FOX gene mutation and abnormal expression exist in cancer,but the occurrence and development of FOX gene family in pan-cancer are not clear.Here,we explores the molecular characteristics of FOX gene families in different cancers by integrating multi-omics data from the pan-cancer genome,transcriptome,and epigenome to provide a scientific basis for revealing the role of FOX genes in cancer progression,using survival analysis,drug sensitivity analysis,and other statistical methods to resolve the potential functions of FOX gene families and provide new ideas for early diagnosis and selection of treatment options for cancer.Methods: The frequencies of somatic mutation and copy number variation of FOX gene family in 33 cancers were calculated by integrating the multi-omics data of The Cancer Genome Atlas(TCGA).Differential expression analysis of TCGA pancancer expression profiles was performed using the Limma package in the R program.Pearson correlation coefficient was used to measure the correlation of gene expression among FOX gene family members.Information on target genes regulated by the FOX gene family was collected from the Ch IP-Atlas database to analyze whether the differences in expression of target genes were significant in different cancers,and correlation analysis was performed between FOX genes and target genes to identify the biological pathways in which the target genes were involved.Meanwhile,the association between FOX gene family expression and prognosis of cancer patients was investigated by COX regression analysis,and the relationship between the FOX gene family expression and drug sensitivity was analyzed based on the half-inhibitory concentration(IC50)data of cancer cell line drugs downloaded from the Genomics of drug sensitivity in cancer(GDSC)database.Results: Genomic analysis revealed widespread mutations and copy number variation in the FOX gene family in pan-cancer.Differential expression analysis revealed that the FOX gene family was commonly differentially expressed in cancer and normal samples and showed similar expression patterns in different subtypes of the same cancer,and its dysregulation was regulated by multiple factors.Pearson correlation analysis revealed extensive synergistic regulation among FOX gene family members.Information on 12,607 target genes regulated by 20 FOX gene family members was collected from the Ch IP-Atlas database,and it was found that the expression of target genes differed significantly across cancers and correlated significantly with FOX gene family members,and that the target genes were also involved in DNA metabolic processes,chromatin organization,and other biological pathways.In addition,survival analysis revealed that the expression levels of FOX gene family members were associated with overall patient survival,with FOXM1 being a risk factor for survival in 12 cancers and nearly half of the FOX gene family members in KIRC being significantly associated with their survival.Drug sensitivity analysis identified the interaction between 103 FOX genes-drugs-drug target genes-related signal pathways,and confirmed that FOX genes play a key role in cancer development.Finally,integrating the results of this study,we developed an online multi-omics resource platform for tumor FOX gene families and named it FOX2 Cancer.Conclusion: This study systematically analyzed the multi-omics global landscape of 49 FOX genes in pan-cancer from different perspectives,including somatic mutations,copy number variants,expression patterns,cancer prognosis and drug sensitivity,by integrating multi-omics data resources to provide new insights into the pathogenesis of tumors and identification of potential molecular markers.The FOX2 Cancer database developed based on the results of this analysis is expected to be a powerful tool for studying the multi-omic molecular features of FOX gene family of pan-cancer.