Abstract
BackgroundThe aim of this study was to identify novel genes in promoting primary prostate cancer (PCa) progression and to explore its role in the prognosis of prostate cancer.MethodsFour microarray datasets containing primary prostate cancer samples and benign prostate samples were downloaded from Gene Expression Omnibus (GEO), then differentially expressed genes (DEGs) were identified by R software (version 3.6.2). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to identify the function of DEGs. Using STRING and Cytoscape (version 3.7.1), we constructed a protein-protein interaction (PPI) network and identified the hub gene of prostate cancer. Clinical data on GSE70770 and TCGA was collected to show the role of hub gene in prostate cancer progression. The correlations between hub gene and clinical parameters were also indicated by cox regression analysis. Gene Set Enrichment Analysis (GSEA) was performed to highlight the function of Ubiquitin-conjugating enzyme complex (UBE2C) in prostate cancer.Results243 upregulated genes and 298 downregulated genes that changed in at least two microarrays have been identified. GO and KEGG analysis indicated significant changes in the oxidation-reduction process, angiogenesis, TGF-beta signaling pathway. UBE2C, PDZ-binding kinase (PBK), cyclin B1 (CCNB1), Cyclin-dependent kinase inhibitor 3 (CDKN3), topoisomerase II alpha (TOP2A), Aurora kinase A (AURKA) and MKI67 were identified as the candidate hub genes, which were all correlated with prostate cancer patient’ disease-free survival in TCGA. In fact, only UBE2C was highly expressed in prostate cancer when compared with benign prostate tissue in TCGA and the expression of UBE2C was also in parallel with the Gleason score of prostate cancer. Cox regression analysis has indicated UBE2C could function as the independent prognostic factor of prostate cancer. GSEA showed UBE2C had played an important role in the pathway of prostate cancer, such as NOTCH signaling pathway, WNT-β-catenin signaling pathway.ConclusionsUBE2C was pivotal for the progression of prostate cancer and the level of UBE2C was important to predict the prognosis of patients.
Highlights
Prostate cancer has become the most universal diagnosed cancer among American men, which accounted for 20% of newly diagnosed cancers [1,2]
Four microarray datasets containing primary prostate cancer samples and benign prostate samples were downloaded from Gene Expression Omnibus (GEO), differentially expressed genes (DEGs) were identified by R software
UBE2C, PDZbinding kinase (PBK), cyclin B1 (CCNB1), Cyclin-dependent kinase inhibitor 3 (CDKN3), topoisomerase II alpha (TOP2A), Aurora kinase A (AURKA) and MKI67 were identified as the candidate hub genes, which were all correlated with prostate cancer patient’ diseasefree survival in The Cancer Genome Atlas [24] (TCGA)
Summary
Prostate cancer has become the most universal diagnosed cancer among American men, which accounted for 20% of newly diagnosed cancers [1,2]. Among American men, prostate cancer remained the third-leading reason for cancer death. From 2000 to 2011, the occurrence of prostate cancer has increased year by year. Prostate cancer has become a threat to long-term health of patients and has worsened the living conditions. In China, the mortality of prostate cancer has been rising year by year too. Androgen deprivation therapy(ADT) combined with radiotherapy was superior to other therapies for high risk prostate cancer patients [4]. The aim of this study was to identify novel genes in promoting primary prostate cancer (PCa) progression and to explore its role in the prognosis of prostate cancer.
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