■胶质母细胞瘤是最具侵袭性和最致命的恶性肿瘤之一。获得性耐药性降低了贝伐单抗在胶质母细胞瘤治疗中的有效性,从而增加了胶质母细胞瘤患者的死亡率。在这项研究中,pentagamavunone-1(PGV-1)的潜在目标,姜黄素类似物,在胶质母细胞瘤治疗中作为贝伐单抗的补充治疗进行了探索。
■目标预测,数据收集,并使用相似性集成方法(SEA)进行分析,SwissTargetPrediction,STRINGDB,和基因表达综合(GEO)数据集。使用Webgestalt和DAVID进行了基因本体论和京都基因和基因组百科全书(KEGG)途径富集分析,分别。使用CytoHubba基于最高程度分数选择Hub基因。用cBioportal和GEPIA进行遗传改变和基因表达的分析以及所选基因的Kaplan-Meier存活分析。用数据库TIMER2.0分析所选基因和免疫细胞之间的免疫浸润相关性。
■我们发现374个PGV-1靶标,1139个差异表达基因(DEG)来自贝伐单抗耐药的胶质母细胞瘤细胞。使用这两组数据的维恩图分析产生21个基因,其被鉴定为针对贝伐单抗抗性(PBR)的PGV-1的潜在靶标。PBR通过细胞色素P450调节外源性物质的代谢。七个潜在的治疗PBR,发现GSTM1,AKR1C3,AKR1C4,PTGS2,ADAM10,AKR1B1和HSD17B110在1.2%-30%的胶质母细胞瘤患者中具有遗传改变。使用GEPIA数据库的分析表明,胶质母细胞瘤患者ADAM10,AKR1B1和HSD17B10的mRNA表达显着上调。Kaplan-Meier生存分析显示,只有AKR1B1mRNA低表达患者的总生存率明显优于高mRNA组患者。我们还发现了PBR与免疫细胞之间的相关性,因此揭示了PGV-1通过靶向PBR作为免疫治疗剂的潜力。
■这项研究强调了七个PBR,即,GSTM1、AKR1C3、AKR1C4、PTGS2、ADAM10、AKR1B1和HSD17B110。该研究还强调了PBR作为PGV-1免疫疗法靶标的潜力。PGV-1作为胶质母细胞瘤免疫治疗的辅助手段,以抵消贝伐单抗耐药性,需要进一步验证这项研究的结果。
UNASSIGNED: Glioblastoma is one of the most aggressive and deadliest malignant tumors. Acquired resistance decreases the effectiveness of bevacizumab in glioblastoma treatment and thus increases the mortality rate in patients with glioblastoma. In this study, the potential targets of pentagamavunone-1 (PGV-1), a curcumin analog, were explored as a complementary treatment to bevacizumab in glioblastoma therapy.
UNASSIGNED: Target prediction, data collection, and analysis were conducted using the similarity ensemble approach (SEA), SwissTargetPrediction, STRING DB, and Gene Expression Omnibus (GEO) datasets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using Webgestalt and DAVID, respectively. Hub genes were selected based on the highest degree scores using the CytoHubba. Analysis of genetic alterations and gene expression as well as Kaplan-Meier survival analysis of selected genes were conducted with cBioportal and GEPIA. Immune infiltration correlations between selected genes and immune cells were analyzed with database TIMER 2.0.
UNASSIGNED: We found 374 targets of PGV-1, 1139 differentially expressed genes (DEGs) from bevacizumab-resistant-glioblastoma cells. A Venn diagram analysis using these two sets of data resulted in 21 genes that were identified as potential targets of PGV-1 against bevacizumab resistance (PBR). PBR regulated the metabolism of xenobiotics by cytochrome P450. Seven potential therapeutic PBR, namely GSTM1, AKR1C3, AKR1C4, PTGS2, ADAM10, AKR1B1, and HSD17B110 were found to have genetic alterations in 1.2%-30% of patients with glioblastoma. Analysis using the GEPIA database showed that the mRNA expression of ADAM10, AKR1B1, and HSD17B10 was significantly upregulated in glioblastoma patients. Kaplan-Meier survival analysis showed that only patients with low mRNA expression of AKR1B1 had significantly better overall survival than the patients in the high mRNA group. We also found a correlation between PBR and immune cells and thus revealed the potential of PGV-1 as an immunotherapeutic agent via targeting of PBR.
UNASSIGNED: This study highlighted seven PBR, namely, GSTM1, AKR1C3, AKR1C4, PTGS2, ADAM10, AKR1B1, and HSD17B110. This study also emphasized the potential of PBR as a target for immunotherapy with PGV-1. Further validation of the results of this study is required for the development of PGV-1 as an adjunct to immunotherapy for glioblastoma to counteract bevacizumab resistance.