甲状腺乳头状癌组织中E74样ETS转录因子3表达上调的临床意义OA

Objective To analyze the abnormal expression and clinical significance of E74-like ETS transcription factor 3(ELF3)in papillary thyroid carcinoma(PTC).Methods Nine PTC samples were collected from the First Affiliated Hospital of Guangxi Medical University.The PTC tissues were used as the experimental group,and the corresponding adjacent tissues were used as the control group.Four tissue chips(THC481,THC961,THC1021 and THC1501)were purchased from Guilin Fanpu Biotech,Inc.,including 45 non-cancerous thyroid tissues and 136 PTC tissues.The expression level of ELF3 protein was detected by immunohistochemistry.The expression of ELF3 mRNA was evaluated based on PTC-related gene chips and RNA-seq data in GEO,TCGA and GTEx databases.The cBioPortal database was used to query the genetic changes of ELF3 in PTC.By combining the target genes of ELF3,the up-regulated differentially expressed genes in PTC and the co-expressed genes of ELF3,enrichment analysis and protein-protein interaction(PPI)analysis were performed to explore the possible signaling pathways and target genes of ELF3 in PTC.Results Immunohistochemistry results showed that ELF3 protein expression in PTC tissues(n=145)was significantly higher than that in adjacent non-cancerous tissues(n=54)(P＜0.001).Consistent with the protein level,ELF3 mRNA expression was upregulated in PTC tissues(n=1136)compared with adjacent non-cancerous tissues(n=778),with a standardized mean difference of 0.44(95%CI:0.25-0.62,P=0.019),and the area under the receiver operating characteristic curve was 0.68(95%CI:0.64-0.72).Data from cBioPortal indicated that ELF3 gene alterations were present in 6%of PTC cases.Enrichment analysis revealed that the candidate target genes of ELF3 might be involved in biological processes such as signal transduction,cell adhesion,and apoptotic process,participate in cellular components including plasma membrane,membrane,and cytosol,and exert molecular functions such as protein binding.Furthermore,it was observed that ELF3 might be associated with cytokine-cytokine interactions and the MAPK signaling pathway.By constructing a PPI network combined with ChIP-seq data,two potential target genes of ELF3,namely FN1 and ICAM1,were identified,and the expression of ELF3 showed a strong positive correlation with FN1 and ICAM1.Conclusion The up-regulation of ELF3 may play an important role in the occurrence and development of PTC,which may be achieved by ELF3 regulating downstream target genes FN1 and ICAM1.