scholarly journals Identification of castration‐resistant prostate cancer‐related hub genes using weighted gene co‐expression network analysis

2020 ◽  
Vol 24 (14) ◽  
pp. 8006-8017 ◽  
Author(s):  
Yifei Cheng ◽  
Lu Li ◽  
Zongshi Qin ◽  
Xiao Li ◽  
Feng Qi
2019 ◽  
Author(s):  
Zhongxiang Yu ◽  
Hanlin Zou ◽  
Huihao Wang ◽  
Qi Li ◽  
Dong Yu

Abstract Background About 80-90% of castration-resistant prostate cancer (CRPC) patients would develop bone metastasis, which leads to the disorder of bone metabolism and induces skeletal related events. However, except for the few approved radiotherapeutic and chemotherapy drugs, like radium-223 and denosumab, there is still lack of effective treatment targeting the bone metastatic tumor. It is necessary and significant to explore the mechanisms of bone metastasis and tumorigenesis, especially the differences between the tumor and normal cells in bone after metastatic colonization, which will provide a set of candidate genes for the screening of novel bone targeting agents.Results 4 datasets (GSE32269, GSE101607, GSE29650 and GSE74685) were obtained from the GEO database. 1983 differentially expressed genes (DEGs) were first identified between bone marrow tumor samples and normal marrow samples in GSE32269, followed by the weighted gene co-expression analysis. Most of the top 10 DEGs are found to be related with prostate cancer. 7 co-expression modules were then detected based on the 1469 DEGs shared by the 4 datasets, and 3 of them were found highly preserved among the other three datasets. The top 30 hub genes of the 3 modules were extracted. Among the enriched pathways of preserved modules, Cell adhesion molecules (CAMs) and Leukocyte transendothelial migration might play significant important roles in the tumor development in bone marrow. Literature searches further showed that a set of DEGs and hub genes might also contribute to the development of tumor in bone.Conclusions Together, our findings not only provide outline of expression profile in CRPC bone metastasis, but also screen a set of genes associated with CPRC tumor cell colonization and development of bone tumor, which could be helpful for novel bone targeting agents screening.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11133
Author(s):  
Zhengquan Xu ◽  
Yanhong Ding ◽  
Wei Lu ◽  
Ke Zhang ◽  
Fei Wang ◽  
...  

Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage and the leading cause of death in prostate cancer patients, among which bone metastasis is the most common site. Here in this article, we downloaded the gene expression data and clinical information from online dataset. We found that prostate cancer metastasis in bone is prone to have higher prostate-specific antigen (PSA) and longer time on first-line androgen receptor signaling inhibitors (ARSI). A total of 1,263 differentially expressed genes (DEGs) were identified and results of functional enrichment analysis indicated the enrichment in categories related to cell migration, cancer related pathways and metabolism. We identified the top 20 hub genes from the PPI network and analyzed the clinical characteristics correlated with these hub genes. Finally, we analyzed the immune cell abundance ratio of each sample in different groups. Our results reveal the different clinical characteristics, the immune cell infiltration pattern in different sites of mCRPC, and identify multiple critical related genes and pathways, which provides basis for individualized treatment.


2021 ◽  
pp. 1-15
Author(s):  
Caibin Fan ◽  
Wei Lu ◽  
Kai Li ◽  
Chunchun Zhao ◽  
Fei Wang ◽  
...  

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage of prostate cancer and the main cause of morbidity and mortality, which is also a potential target for immunotherapy. METHOD: In this study, using the Approximate Relative Subset of RNA Transcripts (CIBERSORT) online method, we analysed the immune cell abundance ratio of each sample in the mCRPC dataset. The EdgeR (an R package) was used to classify differentially expressed genes (DEGs). Using the Database for annotation, visualisation and interactive exploration (DAVID) online method, we performed functional enrichment analyses. STRING online database and Cytoscape tools have been used to analyse protein-protein interaction (PPI) and classify hub genes. RESULTS: The profiles of immune infiltration in mCRPC showed that Macrophages M2, Macrophages M0, T cells CD4 memory resting, T cells CD8 and Plasma cells were the main infiltration cell types in mCRPC samples. Macrophage M0 and T cell CD4 memory resting abundance ratios were correlated with clinical outcomes. We identified 1102 differentially expressed genes (DEGs) associated with the above two immune cells to further explore the underlying mechanisms. Enrichment analysis found that DEGs were substantially enriched in immune response, cell metastasis, and metabolism related categories. We identified 20 hub genes by the protein-protein interaction network analysis. Further analysis showed that three critical hub genes, CCR5, COL1A1 and CXCR3, were significantly associated with prostate cancer prognosis. CONCLUSION: Our findings revealed the pattern of immune cell infiltration in mCRPC, and identified the types and genes of immune cells correlated with clinical outcomes. A new theoretical basis for immunotherapy may be given by our results.


2019 ◽  
Author(s):  
Mitchell G Lawrence ◽  
Laura H Porter ◽  
Daisuke Obinata ◽  
Shahneen Sandhu ◽  
Luke A Selth ◽  
...  

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