The Expression And Mechanism Of Transcription Factor FOXM1 And Its Target Gene IL24 In Esophageal Squamous Cell Carcinoma

Objective: Esophageal cancer is an aggressive malignant tumor of the upper gastrointestinal tract.It is the seventh most common carcinoma in the world and the sixth leading cause of tumor-related deaths.Esophageal squamous cell carcinoma(ESCC)accounts for nearly 90% of esophageal cancer cases in our country.Although neoadjuvant chemotherapy,local surgery,radiotherapy and chemotherapy have made clinical progress,the overall survival of ESCC is still unsatisfied,and the 5-year survival rate rarely exceeds 20%.This is mainly related to the late diagnosis and metastasis of ESCC.Therefore,it is great significance for the clinical treatment and prognostic evaluation of ESCC to explore molecular markers related to the occurrence,development and prognosis of ESCC tumors.At present,there are few studies on the transcription factor forkhead box protein M1(FOXM1)in ESCC,and its role and related mechanisms in ESCC are not yet clear.Therefore,the objective of this research is to:(1)clarify the expression of transcription factor FOXM1 in ESCC and its clinical practice significance;(2)clarify whether FOXM1 has the potential to become an important biomarker for ESCC diagnosis,treatment and prognosis;(3)explore the specific target of transcription factor FOXM1 and its potential molecular mechanism in ESCC;(4)clarify the target of FOXM1 expression and clinical significance in ESCC.Materials and Methods: High-throughput RNA sequencing(RNA-seq)and tissue chip immunohistochemistry were used to detect the mRNA and protein expression levels of FOXM1.Then the cancer genome atlas(TCGA)joint the Genotype-Tissue Expression(GTEx)database and the Gene Expression Omnibus(GEO)database were used to analyze and verify the expression of FOXM1.Through meta-analysis,the expression level and diagnostic value of FOXM1 in ESCC were analyzed by multi-center comprehensive calculation.The Cistrome DB database was used to predict the target genes of FOXM1,and the potential target genes of FOXM1 were applied for biological function and pathway analysis and protein interaction network analysis,and the core target gene was screened out from PPI network.Then,the transcription factor FOXM1 and its hub gene were verified by the Cistrome DB database.Similarly,the expression and clinical significance of FOXM1 hub gene in ESCC were analyzed by combining RNA-seq and tissue chip immunohistochemistry of our hospital with the results of RNA-seq and gene chip of public databases.Results: The 8 high-throughput RNA-seq of ESCC tissue samples,tissue chip immunohistochemistry,RNA-seq results of TCGA combined with GTEx database and the results of multiple gene chips of GEO database all confirmed the overexpression status of FOXM1 in ESCC tissues.We also analyzed the clinical value of FOXM1 in ESCC through the clinical data in the existing data set.The results showed that the expression of FOXM1 was significantly aberrant in different ages,genders,pathological stages,T stages and N stages.In the prognostic analysis,we found that the prognosis of patients with high FOXM1 expression in ESCC patients is better than that of patients with low expression.Signal pathway analysis of the potential target genes of FOXM1 found that they are mainly enriched in the extracellular matrix(ECM)and cell cycle signaling pathways,and the core target gene IL24 of FOXM1 was screened out through further PPI analysis.The results of the synthesis of RNA-seq in our hospital,tissue chip immunohistochemistry,TCGA-GTEx and GEO public database of ESCC tissues confirmed that the mRNA and protein expression levels of IL24 were significantly increased in ESCC tissues.And the expression of IL24 in ESCC patients without metastasis was significantly higher than that in patients with distant metastasesConclusion: FOXM1 mRNA and protein expression levels are significantly increased in ESCC,and this overexpression trend is also closely related to the age,gender,tumor stage,regional lymph node metastasis and distant metastasis of ESCC patients.FOXM1 may play a role in the occurrence and development of ESCC and other biological processes by regulating the ECM and cell cycle pathways mediated by its target gene IL24.IL24 mRNA and protein levels are significantly overexpressed in ESCC tissues,and the differential expression of IL24 in ESCC patients is closely related to whether ESCC patients have distant metastasis.