Expression Of DLX1 In Lung Adenocarcinoma Cells And Its Clinical Significance

Objective(s):More and more evidence shows that non-distal homeobox gene 1(DLX1)is involved in the occurrence and development of various tumors.Some studies have shown that non-distal homeobox gene 1(DLX1)is a member of the DLX homeobox gene family.Although the DLX homeobox gene family does not exist in most normal adult tissues,the DLX homeobox gene family is widely expressed in leukemia,breast cancer,ovarian cancer and prostate cancer,and is associated with poor prognosis.However,there are few reports that the expression of nondistal homeobox gene 1(DLX1)in lung adenocarcinoma is related to tumor prognosis and immune infiltration.In this study,we aim to explore the prognostic and immunological effects of non-distal homeobox gene 1(DLX1)in lung adenocarcinoma(LUAD),and may provide important information for the development of immunotherapy.Methods:We analyzed the expression of DLX1 in various cancers,including lung adenocarcinoma,from the Cancer Genome Map(TCGA)database.The R package was used to analyze the RNA sequencing data to determine the differentially expressed genes(DEGs)between lung adenocarcinoma tissues with high and low expression of DLX1 in TCGA-LUAD database.Spearman correlation analysis was used to determine the relationship between DLX1 expression and immune cell infiltration and immune infiltration score(TMEscore).Meth Surv and CBio Portal databases methylation database were used to analyze the methylation and gene changes of DLX1 gene.The relationship between the expression of DLX1 and the clinicopathological features of patients with lung adenocarcinoma was analyzed by Logistic regression.Kaplan-Meier survival curve,ROC curve,nomogram model and Cox regression analysis were used to evaluate the diagnostic and prognostic value of DLX1.The biological function of DLX1 is determined by gene ontology(GO)and gene and genomics(KEGG)respectively.Finally,the expression level and biological function of DLX1 in LUAD were determined by q PCR,CCK8,Transwell and wound healing test.Results:DLX1 was increased in most cancers.DLX1 m RNA expression was significantly increased in lung adenocarcinoma compared to adjacent normal tissues.the TCGA database and Kaplan-Meier mapper database showed that higher DLX1 expression levels were associated with poor prognostic survival in LUAD.In addition,Cox regression analysis showed that DLX1 was a potential independent risk factor for overall survival(OS),disease-specific survival(DSS)and progression-free interval(PFI)in LUAD patients.DEGs associated with DLX1 were significantly enriched in the cell proliferation pathway.In LUAD tissues,DLX1 expression levels were significantly correlated with immune cell infiltration and tumor mutational load.The DNA methylation status of the two Cp G islands of the DLX1 gene was associated with prognosis in LUAD.DLX1 expression levels in LUAD tissues were associated with tumor stage,overall survival,disease-specific survival and progression-free interval.ROC curve analysis showed that DLX1 QRT-PCR showed that DLX1 was upregulated in LUAD cell lines.By knocking down DLX1,cell proliferation,migration and invasion of LUAD cells were inhibited.Conclusion(s):The results of bioinformatics analysis showed that the lung adenocarcinoma patients with high expression of DLX1 were closely related to pathological stage and poor prognosis events(OS,DSS,PFI),and the prognosis was related to the methylation of DLX1.Secondly,DLX1 may regulate the occurrence and progression of lung adenocarcinoma by regulating the expression of genes involved in cell cycle and immune response.The expression level of DLX1 is related to the tumor infiltration of many immune cells and may play a role in immunotherapy in patients with lung adenocarcinoma.Compared with normal lung epithelial cells,the expression of DLX1 in lung adenocarcinoma cells was increased,and the biological functions of knock-down DLX1 lung adenocarcinoma cell lines A549 and H1299 were significantly inhibited,including proliferation,migration and invasion.It is suggested that DLX1 may play the role of proto-oncogene in lung adenocarcinoma and is a potential biomarker for diagnosis and prognosis in lung adenocarcinoma.