| Objectives We extract the important differentially expressed proteins(DEPs), biological processes and signaling pathways related with tumor through overall mining and a bioinformatics analysis of proteomics literature in prostate cancer(PCa), which would provide more diversified clues and basis to further investigate the molecular mechanisms of PCa carcinogenesis and development and clinical targeted therapy.Methods 1 We used PubMed as the main source for the literature search and restricted the search to studies published in English before June 1, 2015. We divided the selected proteomics literature into two groups: the PCa and benign tissue or cell(P&b) group and the high and low metastatic tendency of PCa(H&L) group. 2 We manually extracted all DEPs in the literature and transformed it into corresponding official gene symbols. We counted the frequency with which each DEP is reported in the literature and carried out a GO(Gene Ontology) enrichment analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes) pathway analysis of the DEPs from the P&b and H&L groups. 3 We selected the DES protein, which was the most commonly reported protein in the P&b group, for further experimental validation. A total of 60 pathological sections were postoperatively collected from each patient at the department of Pathology of the North China University of Science and Technology Affiliated Hospital. These patients were divided into the PCa group, which included 30 patients who had undergone a transurethral resection of the prostate between 2007 and 2014. The remaining 30 patients were allocated to the BPH group. We searched the literature for DEPs that had been reported more than three times in the P&b and H&L groups to study the molecular mechanisms by which these proteins are involved in PCa. 4 We used the Pub Med Database as the main source for literature retrieval and updated the time before July 26 th, 2015. We extracted the DEPs again and identified 41 DEPs verified or reported more than 2 times from different research studies. We regarded these proteins as seed proteins to construct a protein-protein interaction PPI network. The backbone network and the subnetwork were constructed. Topologica l analyses and module analysis of the network were also conducted to identify proteins essential for the genesis of PCa.Results 1 The data mining and analysis identified a total of 555 DEPs. Of the 555 DEPs, 320 were in the P&b group, 353 were in the H&L PCa group, and 119 appeared in both groups. In the P&b group, 77 DEPs were reported more than twice, and 20 were reported more than three times. DES was reported most often(seven times). The association between FGG, GSN, SERPINC1, TPM1, and TUBB4 B and PCa occurrence has not been studied in detail. In the H&L group, 52 proteins were reported more than twice and 13 were reported more than three times. Of these proteins, ACPP, HSPA5, and VCL were reported most often(four times). The association between MDH2 or MYH9 and PCa has not yet been investigated, which warrants further investigation. The immunohistochemical results showed that DES was significantly downregulated in cancer tissues. 2 We conducted GO categories enrichment analysis and KEGG pathway analysis for DEPs in P&b and H&L groups. We identified GO terms for biological processes significantly enriched in response to wounding, regulation of apoptosis, response to organic substance, homeostatic process, cell motion, and cell adhesion in the P&b group in our study. The overrepresented DEPs in the P&b group are mainly related to focal adhesion formation, the complement and coagulation cascades, and the glycolysis/gluconeogenesis signalingpathway. In the H&L group, we identified GO terms for biological processes significantly enriched in protein localization, protein transport, the regulation of apoptosis, cell adhesion, and homeostasis. The overrepresented DEPs are mainly associated with the regulation of the actin cytoskeleton, focal adhesion formation, ECM–receptor interaction, and the complement and coagulation cascade signaling pathways. 3 The extended network included one giant network, which consists of 1264 nodes connected via 1744 edges, and three small separate components. Topological analyses of the giant network, the backbone network and the subnetwork showed that SLC2A4 had the highest closeness centrality located in the center of each network, and the highest betweenness centrality and largest degree in the backbone network. TUBB2 C had the largest degree in the giant network and subnetwork. In addition, using module analysis of the whole network, we obtained a densely connected region. Functional annotation indicated that the module was mainly enriched in the Ras protein signal transduction biological process, MAPK, neurotrophin and the Gn RH signaling pathway.Conclusions 1 The repeatedly reported DEPs(three times or more) between the P&b and H&L groups may serve as potential biomarkers to discriminate PCa from benign tissue or identify metastasis risk. The experimental detection of one of these proteins in clinically relevant sets of samples verified our hypothesis. However, some repeatedly reported proteins lacked detailed studies. 2 Proteins related to homeostasis, the wound-healing response, focal adhesions, and the complement and coagulation pathways may play an important role in the occurrence and development of PCa. DEPs associated with protein transport, regulation of actin cytoskeleton, and the extracellular matrix(ECM)–receptor interaction pathway may involved in the metastasis of PCa and have not yet been studied in detail in this context. 3 As network biomarkers, SLC2A4 and TUBB2 C may mediated important biological processes in the occurrence of PCa. In addition, Ras protein signal transduction and the MAPK signaling pathway may play an important role in the genesis and development of PCa. Further investigation of these proteins, biological processes and pathways could reveal the specific pathogenesis of PCa and develop new targets for clinical treatments. |
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