Chu Man, Ji Huihui, Li Kehan, Liu Hejing, Peng Mengjia, Wang Zhiwei, Zhu Xueqiong
Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, 325027, China.
Discov Oncol. 2023 Sep 13;14(1):170. doi: 10.1007/s12672-023-00788-y.
Cervical cancer is emerging as a potential target of increased susceptibility to coronavirus disease-2019 (COVID-19), leading to compromised survival rates. Despite this critical link, efficacious anti-cervical cancer/COVID-19 interventions remain limited. Quercetin, known for its efficacy against both cancer and viral infections, holds promise as a therapeutic agent. This study aims to elucidate quercetin's anti-cervical cancer/COVID-19 mechanisms and potential targets.
We initiated our investigation with differential gene expression analysis using cervical cancer transcriptome data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx), focusing on intersections with COVID-19-related genes. Network pharmacology was employed to identify the shared targets between cervical cancer/COVID-19 DEGs and quercetin's targets. Subsequently, Cox proportional hazards analyses were employed to establish a risk score based on these genes. Molecular docking techniques were applied to predict quercetin's therapeutic targets and mechanisms for mitigating cervical cancer and COVID-19.
Our findings unveiled 45 potential quercetin targets with anti-cervical cancer/COVID-19 actions. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted significant enrichment in immune pathways and COVID-19-related pathways. A refined risk score model, comprising PLA2G7, TNF, TYK2, F2, and NRP1, effectively stratified cervical cancer patients into distinct risk groups. Importantly, molecular docking analyses illuminated quercetin's remarkable binding affinity to the primary protease of the coronavirus.
In summation, our study suggests that quercetin holds promise as a potential therapeutic agent for mitigating coronavirus function, specifically through its interaction with the primary protease. This research offers novel insights into exploring COVID-19 susceptibility and enhancing survival in cervical cancer patients.
宫颈癌正逐渐成为对2019冠状病毒病（COVID-19）易感性增加的潜在靶点，导致生存率降低。尽管存在这一关键联系，但有效的抗宫颈癌/COVID-19干预措施仍然有限。槲皮素以其对癌症和病毒感染的疗效而闻名，有望成为一种治疗药物。本研究旨在阐明槲皮素的抗宫颈癌/COVID-19机制和潜在靶点。
我们利用来自癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）的宫颈癌转录组数据进行差异基因表达分析，重点关注与COVID-19相关基因的交集，从而启动了我们的研究。采用网络药理学方法识别宫颈癌/COVID-19差异表达基因（DEGs）与槲皮素靶点之间的共同靶点。随后，采用Cox比例风险分析基于这些基因建立风险评分。应用分子对接技术预测槲皮素减轻宫颈癌和COVID-19的治疗靶点和机制。
我们的研究结果揭示了45个具有抗宫颈癌/COVID-19作用的潜在槲皮素靶点。基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析突出了免疫途径和COVID-19相关途径的显著富集。一个由磷脂酶A2G7、肿瘤坏死因子、酪氨酸激酶2、凝血因子Ⅱ和神经纤毛蛋白1组成的精细风险评分模型有效地将宫颈癌患者分为不同的风险组。重要的是，分子对接分析表明槲皮素与冠状病毒的主要蛋白酶具有显著的结合亲和力。
总之，我们的研究表明，槲皮素有望成为一种潜在的治疗药物，通过与主要蛋白酶相互作用来减轻冠状病毒的功能。这项研究为探索COVID-19易感性和提高宫颈癌患者生存率提供了新的见解。
