The Application Of Genomic Information Analysis In Colorectal Cancer Explores The Mechanism Of Action Of ZFHX4

TCGA(The Cancer Genome Atlas)is a public information platform built by NCI(National Cancer Institute)and NHGRI(National Human Genome Research Institute)together.TCGA records different types of clinical information of cancer patients all over the world,genome features data and analysis data of high-throughput sequencing,which provides applicable cases and data for tumor research,especially for tumor genome analysis.Genome Analysis is a statistical analysis technique.With database,it can achieve analysis of data dissimilarity and association,data statistics and survival curve drawing.Meanwhile,it is a vital tool for converting clinical cases into basic research then into clinical application.Nowadays,clinical medicine focuses on evidence-based medicine and preclinical medicine and has a tendency to clinic conversion,which means Genomics Analysis will have a bright future.With the standard of getting died within five years as poor prognosis,the author selected 25 patients among 195 colorectal cancer patients provided by TCGA(colorectal cancer,Nature,2012)basement and conducted statistics and analysis for gene mutation frequency of the tumor samples of them.The author found that the mutation rate of ZFHX4 is 24%(6/25),rating eight among high mutation rate of genes;while,the mutation rate of the rest 170 colorectal cancer patients is 5.3%(9/170),which means the mutation rate of ZFHX4 is higher among those poor-prognosis colorectal cancer patients.Comparing survival curve of those colorectal cancer patients carrying ZFHX4 mutation and none-mutation patients,the author found ZFHX4 mutation can apparently decrease the lifetime of colorectal cancer patients,which shows that ZFHX4 may be a vital factor in prognosis.In order to explore the influence of transcription factor ZFHX4 made during the beginning and the development of tumor,the author conducted gene association study by using the expression level of m RNA based on basement.As a result,the author found that there was positive linear correlation between the expression level of ZFHX4 m RNA and that of CDH2 m RNA,and its correlation coefficient is similar to other transcription factors which were expressed by known direct regulation CDH1 and/or CDH2 expression.N-cadherin,participating inthe development of the nervous system and muscle tissue in embryo,acts as Marker together with E-cadherin during the process of mesenchymal transition.In order to ensure if the target gene regulated and controlled by ZFHX4 is CDH2 and if the target gene participates in the process of mesenchymal transition.With the inducible sh RNA technique,the author found that cell-cell junction was much closer and cell migration ability declined obviously among HCT-116 cell lines whose ZFHX4 lower expression.Comparing expression CDH2 by using Western bolt,the author found that the expression lever of CHD2 got higher obviously after cutting ZFHX4 in HCT-116 which shows ZHFX4 can restrain the expression of CDH2.By using TCGA(colorectal cancer,Nature,2012)basement,ranking the expression level of ZFHX4 and CDH2 collected in tumor cases samples,respectively sorting 1/3(65 people)and 1/4(49 people)of the lowest expression level of ZFHX4 and CDH2 as low expression group and 1/3 cases(65people)and 1/4(49 people)of the highest expression level of ZFHX4 and CDH2 as high expression group,respectively comparing lifetime differences between high and low expression group,the author found the expression differences of ZFHX4 and CDH2 influenced lifetime similarly and the lifetime of high expression group is longer than that of low expression group,but neither of them was up to statistical significance.Along with the increase of the gap between the expression level of ZFHX4 and CDH2,the separation tendency of lifetime differences between the two groups will be more obvious.Genome Analysis is a statistical analysis technique.Its result could appear false-negative,false-positive influenced by a series of factors like the complexity of gene regulation.Therefore,Genome Analysis will provide an important reference for clinical medicine and preclinical medicine.But finally it must be proved and put into use combining with clinical practice and preclinical medicine experiment.