Analysis Of Gene Expression Profile Related Breast Cancer And Its Clinical Prognosis

Research background Latest statistics show,Breast cancer has become the highest incidence and mortality of malignant tumors in the world with a clear trend of younger.The burden of breast cancer is rising rapidly in China,and the share in the world is also increasing.Compared with the western developed countries,where the incidence of the disease has slowed down and the mortality rate has declined,the incidence and mortality of breast cancer in China showed a significant upward trend.In the meanwhile,the survival rate of breast cancer is also lower than that of developed countries.The significant differences in the incidence,mortality and survival of breast cancer between urban and rural areas are the important characteristics of the breast cancer in China.Fortunately,the application of the two generation sequencing technology in 2012 and a series of landmark studies have made a major breakthrough in the study of breast cancer from a genetic perspective.Large scale genomics research has been carried out around the world,to identify genetic alterations in breast cancer,to perfect Breast cancer gene map,to put forward the basis for individualized treatment of breast cancer.Existing research tips that P16,PTEN and ATM genes are the genes that are associated with breast cancer after BRCA1,BRCA2,HER-2 and p53.But the mechanism is unknown,its specific role in dispute.It is well known that recurrence and metastasis are the main factors affecting the prognosis of breast cancer.But the study of prognostic markers of breast cancer is still at the preliminary stage.Previous studies have confirmed that mi RNA-21,mi RNA-210,CXCR4,ALDH1A1,BCL2,and BRCA1/BRCA2 relate to the prognosis of breast cancer.However,the specific mechanism is unknown.Few studies have been done focusing on the prognosis of breast cancer,and the marker of gene level needs to be further confirmed.To sum up,the diagnosis and treatment of breast cancer prevention is grim,and the study of breast cancer gene is of great significance,maybe giving the world's breast cancer patients the gospel.However,there is no clear and effective detection of specific genes to guide the diagnosis and treatment.A large number of studies are needed to screen out some genes with high sensitivity and specificity,and to explore the clinical application value,to provide an important basis for the prevention,early diagnosis,treatment and evaluation of prognosis of breast cancer.Objective This research obtains the sample data from The Cancer Genome Atlas.Through the analysis of the mining,we screened the differentially expressed genes,then acquire some genes with higher sensitivity and specificity by KEGG pathway cluster analysis.At last,to provide an important basis for the prevention and intervention of breast cancer,early diagnosis,treatment and evaluation of prognosis,we explore the clinical value of the genes in clinical prognosis.Methods1.Obtains the sample data in breast cancer from The Cancer Genome Atlas.2.Screen differentially expressed genes by SAM analysis with the conditions: P<0.01,Fold-change>2.3.Research differentially expressed genes associated with tumor signaling pathways by KEGG pathway cluster analysis.4.Screen the differentially expressed genes with high sensitivity and specificity by ROC curve.5.Analyse clinical prognostic relevance of selected genes by Graph Pad Prism6,Log-rank test means to long-term prognosis,Breslow test means to short-term prognosis,P<0.05 shows that the expression level of the gene for the prognosis of patients with significant differences.Results1.Based on the TCGA database,we can get up to 1906 up-regulated genes and 2200 down regulated genes on condition that the fold-change was 2.2.KEGG pathway cluster analysis could be used to screen out 1608 differentially up-regulated genes and 1964 down regulate genes involved in the different tumor signaling pathway.More specifically,up-regulated genes involved in the 25 signaling pathways:Cell cycle,p53 signaling pathway,ECM-receptor interaction,Cell adhesion molecules,Transcriptional misregulation in cancer,DNA replication and so on;down regulate genes involved in the 32 different tumor signaling pathways:c GMP-PKG signaling pathway,Pathways in cancer,P13K-Akt signaling pathways,ECM-receptor interaction,c AMP signaling pathway,Cytokine-cytokine receptor interaction and so on.3.Screen the differentially expressed genes with high sensitivity and specificity by ROC curve;Among them,there were 675 up-regulated genes and 826 down regulated genes.Screen the up-regulated and down regulated genes on condition of fold-change,respectively,to evaluate the diagnostic value in ROC curve.Set the condition of AUC>0.900 for screening diagnosis ability for breast cancer of the up-regulated and down regulated genes.The results were as follows: PTTG1,PLK1,PKMYT1 in the ROC curve among the up-regulated genes with the AUC were >0.900 was high of the diagnostic ability;Correspondingly,PPARG,ZBTB16,RXRG,KIT have better ability in diagnosis.However,the relevance between the expression of genes and the prognosis of patients differ.Conclusions In summary,this study analyzed the expression spectrum of the genes in TCGA database to obtain biological information about breast cancer,and revealed that some differentially expressed genes involved in tumor signaling pathway,with the high sensitivity and specificity,which means that they have good diagnostic potential and breast cancer biological relevance.The high expression of PLK1 is a high-risk factor for the short and long term survival of patients;low expression of KIT is a risk factor for short-term and long-term survival in patients with cancer.So they can be used as a guidance for breast cancer diagnosis,prognosis index evaluation and treatment of prediction.