Screening and validation of diagnosis/prognosis and drug resistance marker in prostate cancer
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Abstract:
Objective: To screen the differentially expressed gene (DEGs) and to identify potential diagnostic/prognostic markers as well as drug resistance markers in prostate cancer (PC) by bioinformatics analysis of published microarray data sets. Methods:Differential expression analyses were performed in available mRNA microarray datasets including prostate cancer tissues dataset GSE6956 and prostate cancer cell taxotere resistance dataset GSE33455 from the GEO database. Gene Ontology enrichment analysis (GO), gene pathway enrichment analysis and protein-protein interaction (PPI) network analysis were performed to identify the biological function and signaling pathways related to DEGs. The expression level of DEGs in PC tissues and para-cancerous tissues was verified by comparing TCGA datasets. Kaplan-Meier method was adopted to detect the influence of DEGs on the survival of PC patients. The expression of DEGs in PC3 cells and taxotere resistant PC3-DTX cells was detected by qPCR. Results: There were a total of 227 genes that differentially co-expressed in taxotere resistant prostate cancer cells and prostate cancer tissues. The functional enrichment analysis showed that these differentially co-expressed genes were mainly enriched in cancer related pathways (Lysosome,Sphingolipid, FoxO, Acute myeloid leukemia) and involved in cell-cell adhesion, autophagy and intracellular protein transportation etc.PPI network screened 18 most connected genes as Hub genes. Among the Hub genes and differentially co-expressed genes, the upregulated CITED2, LRP12 and RPL17-C18orf32 were significantly associated with poor outcomes of PC patients. qPCR validated that CITED2 was upregulated in PC3 and PC3-DTX cells. Conclusion: The present study identified a number of DEGs that differentially co-expressed in prostate cancer tissues and drug resistance cells and significantly associated with the poor prognosis of PC patients by bioinformatical analysis. These results may provide a new idea for identifying potential diagnostic/prognostic and drug resistant markers for prostate cancer.
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Project supported by the National Natural Science Foundation of China (No. 81803564; No. 81670750), and the Postdoctoral Science Foundation Grant of China (No. 2018M633619XB)