School of Pharmacy, Department of Pharmacology, China Medical University, Shenyang, Liaoning 110122, China.
Department of Otolaryngology Head and Neck Surgery, the Sleep Medical Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110122, China.
Biosci Rep. 2021 May 28;41(5). doi: 10.1042/BSR20204148.
Head and neck squamous cell carcinoma (HNSCC) is the most common subtype of head and neck cancer; however, its pathogenesis and potential therapeutic targets remain largely unknown. In the present study, we analyzed three gene expression profiles and screened differentially expressed genes (DEGs) between HNSCC and normal tissues. The DEGs were subjected to gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), protein-protein interaction (PPI), and survival analyses, while the connectivity map (CMap) database was used to predict candidate small molecules that may reverse the biological state of HNSCC. Finally, we measured the expression of the most relevant core gene in vitro and examined the effect of the top predicted potential drug against the proliferation of HNSCC cell lines. Among the 208 DEGs and ten hub genes identified, CDK1 and CDC45 were associated with unfavorable HNSCC prognosis, and three potential small molecule drugs for treating HNSCC were identified. Increased CDK1 expression was confirmed in HNSCC cells, and menadione, the top predicted potential drug, exerted significant inhibitory effects against HNSCC cell proliferation and markedly reversed CDK1 expression. Together, the findings of the present study suggest that the ten hub genes and pathways identified may be closely related to HNSCC pathogenesis. In particular, CDK1 and CDC45 overexpression could be reliable biomarkers for predicting unfavorable prognosis in patients with HNSCC, while the new candidate small molecules identified by CMap analysis provide new avenues for the development of potential drugs to treat HNSCC.
头颈部鳞状细胞癌(HNSCC)是头颈部癌症中最常见的亚型;然而,其发病机制和潜在治疗靶点在很大程度上仍然未知。在本研究中,我们分析了三个基因表达谱,并筛选了 HNSCC 和正常组织之间差异表达的基因(DEGs)。对 DEGs 进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)、蛋白质-蛋白质相互作用(PPI)和生存分析,同时使用连接图谱(CMap)数据库来预测可能逆转 HNSCC 生物学状态的候选小分子。最后,我们在体外测量了最相关核心基因的表达,并研究了顶级预测潜在药物对 HNSCC 细胞系增殖的影响。在 208 个 DEGs 和 10 个核心基因中,CDK1 和 CDC45 与 HNSCC 不良预后相关,确定了三种潜在的治疗 HNSCC 的小分子药物。在 HNSCC 细胞中证实 CDK1 表达增加,预测的潜在药物中名列前茅的 menadione 对 HNSCC 细胞增殖具有显著的抑制作用,并显著逆转 CDK1 的表达。综上所述,本研究确定的 10 个核心基因和途径可能与 HNSCC 的发病机制密切相关。特别是 CDK1 和 CDC45 的过表达可能是预测 HNSCC 患者不良预后的可靠生物标志物,而 CMap 分析确定的新候选小分子为开发治疗 HNSCC 的潜在药物提供了新途径。