The Role Of TNFSF15 In The Occurrence And Development Of Esophageal Cancer And Its Upstream Regulatory Mechanism

Tumor Necrosis Factor Superfamily 15(TNFSF15)is a member of tumor necrosis factor superfamily,which can regulate angiogenesis and inflammation.The expression of TNFSF15 in esophageal carcinoma and its relationship with pathological stage were analyzed using UALCAN.GO and GSVA analysis of TNFSF15 may participate in the function and pathway.The miRNA expression and mRNA methylation data were downloaded from TCGA database.The EWAS Data Hub analyzed the relationship between TNFSF15 methylation site and prognosis.TRANSFAC was used to predict the transcription factors and their effects on the Dual Luciferase activity of TNFSF15 were detected by Dual Luciferase Report Gene experiment.The TNFSF15 genetic variation were genotyped by Polymerase Chain Reaction Restriction Fragment Length Polymorphism(PCR-RFLP).The results show that,TNFSF15 was highly expressed in esophageal carcinoma and was significantly correlated with the early onset of esophageal carcinoma(P<0.05).Enrichment analysis showed that TNFSF15 was involved in a variety of cancer related pathways.The miR-214-5p and miR-374b-5p was abnormal expression in esophageal carcinoma(P<0.05).The TNFSF15 methylation level was decreased(P<0.05),and it was negative correlation with expression level(r=0.3477,P＜0.0001).The cg10791260 was associated with poor prognosis in patients with esophageal cancer.The NF-κB inhibitor significantly reduced the TNFSF15 activity of Dual Luciferase.Compared with TNFSF15-358 TT genotype carriers,the risk of esophageal cancer was increased in-358 CC genotype carriers(or=1.39,95%CI=1.03～1.18,P=0.03).TNFSF15-638A>G genetic variation did not affect the risk of esophageal cancer(P＞0.05).Figure 17;Table 11;Reference 103...