| 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. |
| 多西他赛耐药前列腺癌细胞系的差异基因筛选及功能分析 |
| Differential gene screening and functional analysis in docetaxel-resistant prostate cancer cell lines |
| Received:September 24, 2021 Revised:April 11, 2022 |
| DOI：10.1007/s10330-021-0523-3 |
| 中文关键词: 多西他赛耐药，前列腺癌，差异表达基因，生物信息学，枢纽基因 |
| 英文关键词: docetaxel-resistant; prostate cancer; differentially expressed genes; bioinformatics; hub genes |
| 基金项目:内蒙古自治区自然科学基金项目(No. 2021MS08071);内蒙古自治区卫生和计划生育委员会医疗卫生科研计划项目(No.202202264) |
| 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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| 中文摘要: |
| 目的:虽然多西他赛联合化疗一直是转移性去势难治性前列腺癌(PCa)的标准治疗方法。然而，大多数患者最终对这种治疗产生耐药性，并进一步降低生存率。该研究的目的是使用生物信息学方法确定多西他赛耐药前列腺癌细胞系的关键分子基因。
方法:应用GEO2R对GEO数据库中GSE33455细胞株(包括DU-145/DU-145R和PC-3/PC-3R细胞株)的基因芯片数据进行分析。分别选择DU-145/DU-145R和PC-3/ PC-3R细胞系的差异表达基因(DEGs)，得到两组差异表达基因的交集。通过在线平台(https://cloud)，利用基因本体论(GO)功能对基因进行注释，并利用京都基因和基因组百科全书(KEGG)路径对基因进行丰富。oebiotech.cn/task/detail/arrayenrichment/)。利用在线工具STRING (https://string-db.org/)获取DEGs网络图和矩阵列表，导入Cytoscape 3.6.1中，通过MCODE插件进行分析，检测网络中潜在的功能模块。
结果:在未接受治疗和转化为多西他赛耐药的前列腺癌细胞株之间鉴定了131个交叉的DEGs。氧化石墨烯功能注释显示，参与氧化石墨烯功能的主要基因为质膜、正调控泛素蛋白转移酶活性、正调控伪足组装、中心粒下远端附属物、通过质膜细胞粘附分子介导的嗜异细胞细胞粘附。参与KEGG通路富集的DEGs主要有IL-17信号通路、细胞因子-细胞因子受体相互作用、类风湿性关节炎、军团病和叶酸生物合成。我们确定了两个杰出的deg中心。一种是CD274、CXCL1、DDX58、CXCL2、CXCL8、CSF2、CXCR4、CXCL5、CXCL6。另一种是ASL、ASS1和ASNS。除CXCR4基因表达下调外，其余11个基因表达上调。
结论:某些差异基因可能是预测和治疗转移性多西他赛耐药前列腺癌的潜在靶点。 |
| 英文摘要: |
| 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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