The Bioinformatic Analysis Between Hormone Sensitive And Castration Resistant Prostate Cancer

Background:With the rise of the second-generation sequencing technology and the development and completion of various genomic plans,the genomic data presents a rapid growth trend.In the face of these big data,we need to analyze the method effectively to dig out a lot of information.Biological information mining connects statistics with genomics and clinical information,and selects the most meaningful genes and pathways from a vast amount of information,thus becoming a great tool for scholars.Prostate cancer,the second most common malignancy in men,is a major threat to the health of men.the majority of patients in China with prostate cancer have seen distant metastasis,and endocrine therapy and chemotherapy are particularly important for these patients without radical surgery.Androgen deprivation therapy is widely used in clinical since Huggins and Hodges found androgen dependent characteristics and put forward the endocrine therapy for prostate cancer in 1941,from the initial method of surgical castration to the subsequent drug castration,endocrine therapy got a rapid development.However,we found that some patients have poor response to endocrine therapy in the clinical work,and the disease progresses rapidly.For such patients,timely differential diagnosis is vital importance.But we still can't to identify these patients in terms of the current test methods,so it is necessary to explore some effective biomarkers and method to sensitively identify this kind of patients.Materials and Method:The clinical information and sequencing data of prostate cancer patients were downloaded from the TCGA database(https://portal.gdc.cancer.gov/).And then the Perl software and R language were used to extract different genes(Fold change>2 and P<0.05),and then used cBioPortal website(http://www.cbioportal.org/)to examine the different gene separately through Over Survival-Kaplan Meier Estimate and Diseases free Survival-Kaplan Meier Estimate.Find out different genes that can affect overall Survival time or Disease-Free Survival time(P<0.05).After finding out the final difference genes,we further excavated them including downstream pathway and target gene mining and miRNA interacting with different genes.Result:Total five pairs of samples were found from TCGA dataset and divided into two groups including "YES" group and "NO" group.The RNAseq data of the two groups were analyzed and 97 different genes were obtained.The 97 different genes were analyzed by survival analysis and two genes,SCUBE3 and HOXD8,which could affect the clinical outcome were selected.Then,SCUBE3 and HOXD8 were further excavated by protein interaction network and 10 related genes were obtained respectively.Through further literature analysis,we finally determined HOXD8/ATOH7/EYA2 as a meaningful pathway.As to potential miRNA,we finally got 13 miRNAs for SCUBE3 and 6 ones for HOXD8.Discussion:SCUBE3 and HOXD8 all belong to the protein-coding genes,both the encoded protein is a transcription factor.SCUBE3 plays a role through TGFB pathways and HOXD8 play a crucial regulatory role in the growth of the organism.After reviewing a large number of literatures,we found that ATOH7,a correlation gene of HOXD8,plays a role in retinal nerve cells growth and differentiation through Pax6/ATOH7/EYA2 pathway.ATOH7 is a transcription factor of EYA2 promoter and stimulates the transcription of EYA2,Otherwise,EYA2 is closely associated with ovarian cancer,breast cancer and pancreatic cancer.However,there is no study that describe the relationship between EYA2 and prostate cancer.and the function of ATOH7/EYA2 pathway is still unknown in tumor.So HOXD8(HOX)/ATOH7/EYA2 seem to be a feasible pathway.Moreover,we found that ATOH7 and EYA2 were significantly elevated in patients with prostate cancer.Therefore,after a series of excavations of these five pairs of samples,we believe that SCUBE3 and HOXD8 can be used as bio-marks to identify and predict the endocrine therapy effect and prognosis of patients with prostate cancer.The HOXD8(HOX)/ATOH7/EYA2 pathway is a pathway that may affect the development of prostate cancer,but its specific mechanism still requires further verification of the basic experiment.