Department of Otorhinolaryngology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Inhal Toxicol. 2021 Feb;33(3):113-120. doi: 10.1080/08958378.2021.1908461. Epub 2021 Apr 6.
Reports have shown that formaldehyde (FA) can induce malignant transformation in cells via complicated mechanisms. Therefore, we aimed to investigate the possible molecules, pathways, and therapeutic agents for FA-induced head and neck cancer (HNC) by using bioinformatics approaches.
High throughput data were analyzed to screen the differentially expressed genes (DEGs) between FA-treated nasal epithelium cells and controls. Then, the functions of the DEGs were annotated and the hub genes, as well as the key genes, were further screened out. Afterwards, potential drugs were predicted by using the connectivity map (CMAP) tool.
The information of a microarray-based dataset GSE21477 was extracted and analyzed. A total of 210 upregulated and 83 downregulated DEGs were generated, which might be enriched in various pathways, such as Cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and Toll-like receptor signaling pathway. Among these DEGs, three hub genes including TXNIP, CXCL1, and AREG, were identified as the key genes because they might affect the prognosis of HNC. Finally, a major active ingredient of blister beetles, Cantharidin, was predicted to be one of the potential drugs reversing FA-induced malignant transformation in head and neck epithelium cells.
The present analysis gave us a novel insight into the mechanisms of FA-induced malignant transformation in head and neck epithelium cells, and predicted several small agents for the prevention or treatment of HNC. Future experiment studies are warranted to validate the findings.
已有报道表明,甲醛(FA)可通过复杂机制诱导细胞发生恶性转化。因此,我们旨在通过生物信息学方法研究 FA 诱导的头颈部癌症(HNC)的可能分子、途径和治疗剂。
对高通量数据进行分析,筛选 FA 处理的鼻腔上皮细胞与对照之间的差异表达基因(DEGs)。然后注释 DEGs 的功能,并进一步筛选出枢纽基因和关键基因。之后,使用连接图谱(CMAP)工具预测潜在药物。
提取并分析了基于微阵列的数据集 GSE21477 的信息。共产生了 210 个上调和 83 个下调的 DEGs,这些基因可能富集在各种途径中,如细胞因子-细胞因子受体相互作用、Jak-STAT 信号通路和 Toll 样受体信号通路。在这些 DEGs 中,三个枢纽基因,包括 TXNIP、CXCL1 和 AREG,被确定为关键基因,因为它们可能影响 HNC 的预后。最后,预测斑蝥素(一种水疱甲虫的主要活性成分)可能是逆转 FA 诱导的头颈部上皮细胞恶性转化的潜在药物之一。
本分析为 FA 诱导头颈部上皮细胞恶性转化的机制提供了新的见解,并预测了几种用于预防或治疗 HNC 的小分子药物。未来的实验研究有待验证这些发现。