Correlation Analysis Of DTL Gene And Molecular Typing And Clinicopathological Features Of Breast Cancer

Objective:In this article,the expression of DTL gene in breast cancer,the correlation between DTL expression and breast cancer molecular typing,and clinicopathological features were studied,aiming to discover whether DTL gene can be used as a potential therapeutic target for breast cancer.Methods:The R-pack was used to analyze the pan-cancer RNAseq data in the TCGA database and it was found that the expression of DTL in multiple cancer tissues was markedly higher than that in adjacent tissues.The UALCAN online database was used to verify the expression level of DTLmRNA in BRCA and its relationship with clinicopathological factors;The expression module in bc-Gen Ex Minerv4.2 was used to analyze the relationship between DTLmRNA expression and ER,PR,Her-2,lymph node metastasis,SBR grading,and Nottingham prognostic index;The co-expression genes of DTL were analyzed by Linkedd Omics database,and the co-expression genes with FDR<0.05 were screened for GO and KEGG pathway analysis through the Link Interpreter module,the relationship between DTL genes and immune cell infiltration was further validated and studied by GSEA analysis using R packs.In addition,132 cases of invasive breast cancer and paracancerous tissues were collected to verify the expression of DTL protein in BRCA,and the relationship between it and the molecular typing and clinicopathological features of breast cancer,and further explore the correlation and consistency between DTL protein and the expression of ER,PR,Her-2,Ki67,CK5/6 and EGFR protein.Results:1.In a variety of cancer tissues,DTLmRNA expression levels were higher than those in adjacent tissues(P<0.05).2.In BRCA tissues,the expression level of DTLmRNA was significantly higher than that of adjacent tissues,which was significantly related to breast cancer molecular typing,histological grading,and lymph node metastasis(P<0.001),and the expression levels were higher in the cancerous tissues of ER(-),PR(-)and Her-2(+)(P<0.001),and the expression of DTLmRNA was high in the TNBC group and BRCA with P53mutation(P<0.001).3.KEGG analysis revealed that DTL co-expression genes were mainly enriched in cell cycle,RNA transport,pyrimidine metabolism,cell adhesion molecules,cytokine receptors and other pathways;GO analysis showed that co-expressed genes were mainly involved in chromosome isolation,DNA recombination and RNA localization,extracellular matrix,transport protein complex,histone binding,ATPase activity,and catalytic activity acting on RNA.The GSEA analysis further validates the above conclusions.4.DTLmRNA expression was significantly positively correlated with the infiltration level of immune cells such as helper T cells and Th2 cells,and negatively correlated with the infiltration level of dendritic cells and natural killer cells(P<0.05).5.The results of immunohistochemical experiments were as follows:the expression of DTL protein in BRCA was significantly higher than that of adjacent tissues,and the expression of DTL in TNBC subtype was significantly lower than that of Luminal A,Luminal B and Her-2positive subtypes(P<0.001).The chi-square test analyzed the clinicopathological features and found that DTL expression was significantly correlated with the molecular typing of breast cancer,and the Spearman correlation and consistency test showed that DTL expression was correlated and low consistency with ER,PR and Her-2 expression levels.Conclusions:DTL gene is significantly highly expressed in BRCA,and DTL gene is correlated with breast cancer molecular typing,clinicopathological factors and immune cell infiltration level,which has the potential to become a target for BRCA therapy.