Transcription Factors BARX1 And DLX4 Contribute To Clear Cell Renal Cell Carcinoma Development Via Epithelial-mesenchymal Transition Pathway

Purpose: Dysregulation of transcription factors(TFs)contributes to the carcinogenesis and progression of cancers.However,their roles in clear cell renal cell carcinoma(cc RCC)remain largely unknown.This study aims to evaluate the clinical significance of TFs and investigate their potential molecular mechanisms in cc RCC.Materials and Methods: Data were accessed from the Cancer Genome Atlas Kidney Clear Cell Carcinoma cohort.Bioinformatics algorithm was used in the copy number alterations(CNAs),mutations,and differentially expressed TFs analysis.Univariate and multivariate cox regression were performed to identify clinically significant TFs and construct a six-TF prognostic panel.TFs expression was validated in human tissues by real-time polymerase chain reaction.Gene set enrichment analysis(GSEA)was utilized to find enriched cancer hallmark pathways for TFs.Functional experiments were conducted to verify the cancer-promoting effect of BARX homeobox 1(BARX1)and distal-less homeobox 4(DLX4)in cc RCC and western blot was performed to explore their downstream pathways.Results: A great number of CNAs and mutations were identified in transcription factor(TF)genes.TFs were differentially expressed in cc RCC.An applicable predictive panel of six-TF genes was constructed to predicting overall survival for cc RCC patients,and its diagnostic efficiency was evaluated by the area under the curve(AUC).BARX1 and DLX4 were associated with poor prognosis,and they could promote the proliferation and migration of cc RCC.Conclusions: BARX1 and DLX4 play an oncogenic role in cc RCC via promoting proliferation and epithelial-mesenchymal transition.They carry an important prognostic value and have the potential to be novel therapeutic targets for cc RCC.