关键词: Cervical cancer Drug Pathogenesis Pathway Prognosis Target

来  源:   DOI:10.1186/s44342-024-00008-1

Abstract:
OBJECTIVE: Cervical cancer (CxCa) stands as a significant global health challenge, ranking fourth in cancer-related mortality among the female population. While chemotherapy regimens have demonstrated incremental progress in extending overall survival, the outlook for recurrent CxCa patients remains disheartening. An imperative necessity arises to delve into innovative therapeutic avenues, with molecular targeted therapy emerging as a promising candidate. Previous investigations have shed light on the therapeutic effectiveness of five distinct herbal compounds, epicatechin, curcumin, myricetin, jatrorrhizine, and arborinine, within the context of CxCa.
METHODS: A systems biology approach was employed to discern differentially expressed genes (DEGs) in CxCa tissues relative to healthy cervical epithelial tissues. A protein-protein interaction network (PPIN) was constructed, anchored in the genes related to CxCa. The central genes were discerned within the PPIN, and Kaplan-Meier survival curves explored their prognostic significance. An assessment of the binding affinity of the selected herbal compounds to the master regulator of prognostic markers in CxCa was conducted.
RESULTS: A significant correlation between the overexpression of MYC, IL6, JUN, RRM2, and VEGFA and an adverse prognosis in CxCa was indicated. The regulation of these markers is notably influenced by the transcription factor CEBPD. Molecular docking analysis indicated that the binding affinity between myricetin and the CEBPD DNA binding site was robust.
CONCLUSIONS: The findings presented herein have unveiled pivotal genes and pathways that play a central role in the malignant transformation of CxCa. CEBPD has emerged as a potential target for harnessing the therapeutic potential of myricetin in this context.
摘要:
目标:宫颈癌(CxCa)是一个重大的全球健康挑战,在女性人群中,癌症相关死亡率排名第四。虽然化疗方案在延长总生存期方面表现出了递增的进展,复发性CxCa患者的前景仍然令人沮丧.迫切需要深入研究创新的治疗途径,随着分子靶向治疗成为有希望的候选药物。以前的研究揭示了五种不同的草药化合物的治疗效果,表儿茶素,姜黄素,杨梅素,jatrorrhizine,和arborinine,在CxCa的背景下。
方法:采用系统生物学方法来辨别CxCa组织中相对于健康宫颈上皮组织的差异表达基因(DEGs)。构建了蛋白质-蛋白质相互作用网络(PPIN),锚定在与CxCa相关的基因中。中心基因在PPIN中被识别,和Kaplan-Meier存活曲线探讨了它们的预后意义。对所选择的草药化合物与CxCa中预后标志物的主调节物的结合亲和力进行评估。
结果:MYC的过表达之间存在显着相关性,IL6,JUN,显示RRM2和VEGFA以及CxCa的不良预后。这些标记的调节尤其受到转录因子CEBPD的影响。分子对接分析表明杨梅素与CEBPDDNA结合位点之间的结合亲和力是稳健的。
结论:本文提出的发现揭示了在CxCa的恶性转化中起核心作用的关键基因和途径。在这种情况下,CEBPD已成为利用杨梅素治疗潜力的潜在靶标。
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