BRD4 Gene Function And Molecular Subtypes Of Renal Cell Carcinoma Based On Multiple-omics Data

ObjectiveTo investigate BRD4 gene function and the mechanism of tumor resistance to BRD4 inhibitor JQ1.To study the correlation between the phenotypic markers of renal cell carcinoma(RCC)and the clinical features,to establish a molecular subtype judgment model for RCC,and to analyze the correlation between BRD4 inhibitor JQ1 drug sensitivity related genes and radiomics characteristics.Materials and methodsFirstly,the function of BRD4 gene was analyzed based on the protein database,and the mechanism of BRD4 was discussed through the system biological model in the EBI database.Finally,the function and mechanism of BRD4 were verified by the The Cancer Genome Atlas(TCGA)database.Based on GDSC and CCLE data,the mechanism of tumor resistance to BRD4 inhibitor JQ1 was studied.Radiomics features extracted from radiological phenotype data based on CT and the multilayer perceptron neural network(MLPNN)method was used to establish the prediction model of RCC clinical index and the subtypes of RCC.The correlation between the phenotypic markers of RCC and the clinical characteristics of RCC,such as prognosis,staging,pathological classification,molecular subtypes,and so on,was established.The correlation between radiological characteristics and the expression of genes related to BRD4 inhibitor JQ1 was analyzed.ResultsThe first,we verified the close relationship between the BRD4 gene and transforming growth factor-?(TGF-?)pathway.BRD4 regulates TGF-?signaling pathway through the epigenetic regulation of the phosphorylation of SMAD3 and cell cycle,which is the molecular mechanism of TGF-? pathway plays roles in carcinogenesis and the tumour suppression.Combined with drug data,we also found that the expression of key molecules in the TGF-pathway might be the reason that affects the sensitivity of tumor cells to BRD4 inhibitor JQ1.We found that the imaging features of RCC were correlated with the prognosis,staging and pathological grading of RCC.The molecular subtype of RCC based on MLPNN can be used to identify the molecular subtypes of RCC.Some gene expression related to JQ1 drug sensitivity is correlated with radiological changes.ConclusionWe think BRD4 is a key molecular to determine the two sides of TGF-? pathway at the molecular level.BRD4 regulates TGF-?signaling pathway through the epigenetic regulation of the phosphorylation of SMAD3 and cell cycle,which is the molecular mechanism of TGF-? pathway plays roles in carcinogenesis and the tumour suppression.The TGF-beta pathway is associated with the sensitivity of the BRD4 inhibitor JQ1.The discriminant model of RCC imaging phenotypes based on MLPNN can be used to distinguish the clinical features of RCC,such as prognosis,staging,pathological classification,and the subtype of renal cell carcinoma.Radiogenomics of RCC can find the correlation between the imaging phenotype and gene expression of BRD4 and BRD4 inhibitor JQ1 drug sensitivity related genes,which may guide BRD4 targeted therapy.