Raushan Kumar Chaudhary, Pukar Khanal, Uday Venkat Mateti, C S Shastry, Jayarama Shetty
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The interaction between KEGG pathways and genes was visualized in Cytoscape 3.7.2. Further, the hub gene was identified using the Cytohubba plugin of Cytoscape and validated using UALCAN and Human Protein Atlas database. Validated genes were investigated for the drug-gene interaction using the DGIbd database.</p><p><strong>Results: </strong>Out of 137 genes obtained using key words, 133 were associated with cisplatin resistance in the human species. A total of 150 KEGG pathways, 82 cellular components, 123 molecular functions, and 1752 biological processes were modulated on enrichment analysis. Out of 37 hub genes, CCND1, AXL, CDKN2A, TERT, and EXH2 genes were found to have significant (p < 0.05) mRNA expression and effect on overall survival whereas protein expression was found to be positive for all the significant genes except TERT. Thus, they can be targeted with palbociclib, methotrexate, bortezomib and fluorouracil, sorafenib, dasatinib, carboplatin, paclitaxel, gemcitabine, imatinib, doxorubicin, and vorinostat.</p><p><strong>Conclusion: </strong>As the pathogenesis of head and neck cancer is complex, targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance which might uplift overall survival among HNC patients.</p>","PeriodicalId":74026,"journal":{"name":"Journal, genetic engineering & biotechnology","volume":"21 1","pages":"9"},"PeriodicalIF":3.6000,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886788/pdf/","citationCount":"4","resultStr":"{\"title\":\"Identification of hub genes involved in cisplatin resistance in head and neck cancer.\",\"authors\":\"Raushan Kumar Chaudhary, Pukar Khanal, Uday Venkat Mateti, C S Shastry, Jayarama Shetty\",\"doi\":\"10.1186/s43141-023-00468-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cisplatin resistance is one of the major contributors to the poor survival rate among head and neck cancer (HNC) patients. 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引用次数: 4
摘要
背景:顺铂耐药是头颈癌(HNC)患者生存率低的主要原因之一。关注蛋白质与蛋白质之间的相互作用，而不是单一蛋白质，可以更好地了解耐药性。因此，本研究旨在通过一系列生物信息学工具，在HNC化疗中顺铂耐药相关基因的复杂网络中识别枢纽基因。方法:以“头颈癌”和“顺铂耐药”为关键词，从NCBI基因数据库中检索顺铂耐药相关基因。对检索到的人类基因进行相互作用分析，并使用STRING数据库进行富集。在Cytoscape 3.7.2中可视化了KEGG通路与基因之间的相互作用。此外，利用Cytoscape的Cytohubba插件对枢纽基因进行了鉴定，并使用UALCAN和Human Protein Atlas数据库进行了验证。使用DGIbd数据库研究验证基因的药物-基因相互作用。结果:在关键词检索到的137个基因中，133个基因与人类顺铂耐药相关。富集分析共调控了150条KEGG通路、82个细胞组分、123个分子功能和1752个生物过程。在37个枢纽基因中，CCND1、AXL、CDKN2A、TERT和EXH2基因具有显著性意义(p)。结论:头颈癌发病机制复杂，靶向参与顺铂耐药的枢纽基因及其相关通路，可能会在药物发现和耐药管理方面带来里程碑式的变化，可能会提高HNC患者的总生存率。
Identification of hub genes involved in cisplatin resistance in head and neck cancer.
Background: Cisplatin resistance is one of the major contributors to the poor survival rate among head and neck cancer (HNC) patients. Focusing on the protein-protein interaction rather than a single protein could provide a better understanding of drug resistance. Thus, this study aimed to identify hub genes in a complex network of cisplatin resistance associated genes in HNC chemotherapy via a series of bioinformatic tools.
Methods: The genes involved in cisplatin resistance were retrieved from the NCBI gene database using "head and neck cancer" and "cisplatin resistance" as key words. The human genes retrieved were analyzed for their interactions and enriched using the STRING database. The interaction between KEGG pathways and genes was visualized in Cytoscape 3.7.2. Further, the hub gene was identified using the Cytohubba plugin of Cytoscape and validated using UALCAN and Human Protein Atlas database. Validated genes were investigated for the drug-gene interaction using the DGIbd database.
Results: Out of 137 genes obtained using key words, 133 were associated with cisplatin resistance in the human species. A total of 150 KEGG pathways, 82 cellular components, 123 molecular functions, and 1752 biological processes were modulated on enrichment analysis. Out of 37 hub genes, CCND1, AXL, CDKN2A, TERT, and EXH2 genes were found to have significant (p < 0.05) mRNA expression and effect on overall survival whereas protein expression was found to be positive for all the significant genes except TERT. Thus, they can be targeted with palbociclib, methotrexate, bortezomib and fluorouracil, sorafenib, dasatinib, carboplatin, paclitaxel, gemcitabine, imatinib, doxorubicin, and vorinostat.
Conclusion: As the pathogenesis of head and neck cancer is complex, targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance which might uplift overall survival among HNC patients.
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