| Ming Wang,Lei Wang,Yan Zhang,Chao-Qi Wang,Shuang Li,Tao Fan. Differential gene screening and functional analysis in docetaxel-resistant prostate cancer cell lines. Oncol Transl Med, 2022, 8: 94-99. |
| Differential gene screening and functional analysis in docetaxel-resistant prostate cancer cell lines |
| Received:September 24, 2021 Revised:April 11, 2022 |
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| KeyWord:docetaxel-resistant; prostate cancer; differentially expressed genes; bioinformatics; hub genes |
| Author Name | Affiliation | E-mail | | Ming Wang | Affiliated Hospital of Inner Mongolia University for the Nationalities | | | Lei Wang | Affiliated Hospital of Inner Mongolia University for the Nationalities | | | Yan Zhang | Affiliated Hospital of Inner Mongolia University for the Nationalities | | | Chao-Qi Wang | Affiliated Hospital of Inner Mongolia University for the Nationalities | wangchaoqi001@163.com | | Shuang Li | The People''''s Hospital of China Three Gorges University, The First People''s Hospital of Yichang | | | Tao Fan | Hubei Provincial Hospital of Integrated Chinese and Western Medicine | |
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| Abstract: |
| Objective Docetaxel-based combination chemotherapy has traditionally been the standard treatment for
metastatic castration-resistant prostate cancer (PCa). However, most patients eventually develop resistance
to this treatment, which further reduces their survival. This study aimed to determine key molecular genes in
docetaxel-resistant PCa cell lines using bioinformatic approaches.
Methods The analysis of microarray data GSE33455 (including DU-145/DU-145R and PC-3/PC-3R
cell lines) obtained from the Gene Expression Omnibus (GEO) database was performed using GEO2R.
Differentially expressed genes (DEGs) of DU-145/DU-145R and PC-3/PC-3R cell lines were selected, and
the intersection of DEGs between the two groups was obtained. DEGs were annotated with the Gene
Ontology (GO) function and enriched with the Kyoto Encyclopedia of Genes and Genomes (KEGG)
pathway using an online platform (https://cloud.oebiotech.cn/task/detail/array_enrichment/). The online
tool Search Tool for the Retrieval of Interacting Genes (https://string-db.org/) was used to obtain the DEG
network graph and matrix list, which was imported into Cytoscape 3.6.1 and analyzed using the Molecular
Complex Detection plug-in to detect potential functional modules in the network.
Results A total of 131 intersection DEGs were identified between non-treated and docetaxel-resistant
PCa cell lines. GO functional annotation showed that the main genes involved were present in the plasma
membrane and were involved in positive regulation of ubiquitin-protein transferase activity, positive
regulation of pseudopodium assembly, centriolar subdistal appendage, and heterophilic cell–cell adhesion
via plasma membrane cell adhesion molecules. KEGG pathway enrichment analysis revealed that DEGs
were mainly involved in IL-17 signaling pathway, cytokine-cytokine receptor interaction, rheumatoid
arthritis, legionellosis, and folate biosynthesis. We identified two distinct hubs of DEGs: (1) CD274,
C-X-C motif chemokine ligand (CXCL)1, DExD/H-box helicase 58, CXCL2, CXCL8, colony-stimulating
factor 2, C-X-C motif chemokine receptor 4 (CXCR4), CXCL5, and CXCL6 and (2) argininosuccinate
lyase, argininosuccinate synthase 1, and asparagine synthetase. Except for the CXCR4 gene that was
downregulated, the other 11 genes showed upregulated expression.
Conclusion Certain differential genes may be potential targets for predicting and treating metastatic
docetaxel-resistant PCa. |
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