Target Genes And Function Detected Based On The Prostate Cancer Expression Profiles

Background:Prostate cancer(PC) is the result of acinus cell growth without control. It is the malignancy only developed in males. To date, PC is the most frequent cancer in males in western countries. As the age indication increases and the dietary ingredient changes in Asia and African, the incidence and death rate of prostate cancer raises gradually in the past decades. Although previous studies revealed that prostate cancer progression is a process involving multiple molecular alterations and interactions, the precise molecular mechanisms of prostate cancer remain poorly understood. The development of prostate cancer is because of the instability of genome. Therefore, comparative analysis of gene expression in prostate cancer and benign prostatic specimens may provide important information relating to malignant transformation of prostatic cells. Nowadays, serum PSA is widely used as a diagnostic marker for prostate cancer. PSA has tissue specificity and only found in prostatic acinus and ductal epithelial cells. However, it had no tumor specificity. Sometimes the benign prostatic hyperplasia and prostatitis could detect positive PSA, therefore, it is hard to predict the presence of prostate cancer from benign prostatic hyperplasia and prostatitis. Thus there is an urgent need for identifying new prostate cancer markers. The gene therapy for prostate cancer need the ideal therapeutic targets too. Recently the emerging technology of DNA microarray provide a powerful tool to investigate the gene expression profile of thousands of genes in prostate cancer.Objective:In this present study, we identified the differentially expressed genes between prostate cancer(primary and metastatic) and benign prostate based on DNA microarray. Further, we constructed the regulation networks, protein-protein interaction networks and pathway crosstalk networks to explore the molecular mechanisms of prostate cancer development and progression. We hope our study could aid in detecting the biomarkers of prostate cancer for diagnosis and treatment with prostate cancer.Methods:First, we downloaded the transcription profile of GSE3325from GEO, and performed microarray analysis to screen the differentially expressed genes between prostate cancer (primary and metastatic) and benign prostate. The DEGs only with fold change value larger than2or less than-2and p-value less than0.05were selected.Then we constructed two regulation networks of primary prostate cancer and metastatic prostate cancer by integrating the DEGs and the existing regulation data collected from the database, and analysed the difference of the two networks. In the same way, we constructed the protein-protein interaction networks of primary prostate cancer and metastatic prostate cancer. By calculating the interactive proteins between any two biological pathways, we obtained the interaction significance between any biological pathways.Results:1、There are5847differentially expressed genes between the gene expression profiles of primary prostate cancer and the benign prostate tissue, There are2026differentially expressed genes between the gene expression profiles of metastatic prostate cancer and the benign prostate tissue. Total977genes were overlapping, i.e.,977genes were differentially expressed between metastatic prostate cancer compared with primary prostate cancer.2、We constructed two regulation networks of primary prostate cancer and metastatic prostate cancer by integrating the DEGs and the existing regulation data collected from the database, and performed GO enrichment analysis of genes in the two networks. In the regulation network of primary prostate cancer, the TF MYC with high degree form a local network, and the other TFs, such as E2F1, TP53, ESR1are also hub nodes in the network. In the regulation network of metastatic prostate cancer, the TF MYC plays a vital role as the core of the regulation network.3、We constructed two protein-protein interaction networks of primary prostate cancer and metastatic prostate cancer. By analyzing the difference of the two networks, we found that the interaction between MMP9and IL8only appeared in metastatic prostate cancer. Total775interactions between662proteins only existed in primary prostate cancer.4、Total16significant expressed pathways were identified between primary prostate cancer and benign prostate. The GO enrichment analysis of these16pathways shows that a majority of them are related to cell proliferation and tumorigenesis. Compared to benign prostate, there are8significant expressed pathways in metastatic prostate cancer. Seven out of the8pathways also existed in the primary prostate cancer.