胶质母细胞瘤是原发性脑癌的最常见和侵袭性形式,缺乏可行的治疗方案已经迫切需要开发新的治疗方法。个性化或预测医学目前仍处于起步阶段。这项研究旨在发现生物标志物,以告知疾病进展,并通过结合最先进的技术(如单细胞RNA测序)开发个性化的预防和治疗策略。系统药理学,和多药理学方法。正如在焦亡相关基因(PRG)转录因子(TF)microRNA(miRNA)调控网络中预测的那样,TP53是胶质母细胞瘤(GBM)焦亡过程中的中心基因。建立了焦亡相关基因的LASSOCox回归模型,two-,GBM患者的3年总生存率。得分最高的五种天然化合物是小白菊内酯,芦丁,baeomycceasic酸,木犀草素,还有山奈酚,具有NFKB抑制作用,抗氧化剂,脂氧合酶抑制,葡萄糖苷酶抑制,和雌激素受体激动特性,分别。相比之下,对天然化合物的细胞类型特异性差异表达相关靶标的分析表明,天然化合物靶向的前五名亚型细胞是内皮细胞,小胶质细胞/巨噬细胞,少突胶质细胞,树突状细胞,和中性粒细胞。当前的方法-使用联合疗法的药物基因组学分析-作为GBM治疗的新型个性化治疗策略的模型。
Glioblastoma is the most common and aggressive form of primary brain cancer and the lack of viable treatment options has created an urgency to develop novel treatments. Personalized or predictive medicine is still in its infancy stage at present. This research aimed to discover biomarkers to inform disease progression and to develop personalized prophylactic and therapeutic strategies by combining state-of-the-art technologies such as single-cell RNA sequencing, systems pharmacology, and a polypharmacological approach. As predicted in the pyroptosis-related gene (PRG) transcription factor (TF) microRNA (miRNA) regulatory network, TP53 was the hub gene in the pyroptosis process in glioblastoma (GBM). A LASSO Cox regression model of pyroptosis-related genes was built to accurately and conveniently predict the one-, two-, and three-year overall survival rates of GBM patients. The top-scoring five natural compounds were parthenolide, rutin, baeomycesic acid, luteolin, and kaempferol, which have NFKB inhibition, antioxidant, lipoxygenase inhibition, glucosidase inhibition, and estrogen receptor agonism properties, respectively. In contrast, the analysis of the cell-type-specific differential expression-related targets of natural compounds showed that the top five subtype cells targeted by natural compounds were endothelial cells, microglia/macrophages, oligodendrocytes, dendritic cells, and neutrophil cells. The current approach-using the pharmacogenomic analysis of combined therapies-serves as a model for novel personalized therapeutic strategies for GBM treatment.