Department of Neurosurgery, Third Affiliated Hospital, Navy Medical University, Shanghai, China 200432.
Department of Medical Psychology, The Fourth Medical Center of PLA General Hospital, 51 Fu Cheng Road, Beijing, China 100048.
Dis Markers. 2023 Feb 18;2023:7146589. doi: 10.1155/2023/7146589. eCollection 2023.
The most prevalent malignant tumor in a human brain nervous system is called glioma. Peptide is a compound formed by the peptide bond of -amino acids, and the development of polypeptide drugs has been widely used in many fields. We plan to investigate the underlying peptides with clinical value in glioma.
Based on public databases, we targeted the common genes between glioma differentially expressed genes (DEGs) and peptide genes related to glioma prognosis. Then, these common genes were analyzed by LASSO-Cox analysis, prognostic risk model, and nomogram to identify key prognostic peptide genes and the target gene in this study. Next, the mechanism of target gene in glioma was explored by bioinformatics analysis and functional experiments.
We obtained a total of 26 overlapping genes for the following study. After that, 6 independent prognostic factors (REPIN1, PSD3, RDX, CDK4, FANCI, and ARHGEF9) were obtained and applied to construct the prognostic nomogram, and ARHGEF9 was the target gene in the study. Next, peptide ARHGEF9 was found to inhibit glioma cell development. Through Spearman's correlation analysis, ARHGEF9 had a close relation with PI3K/AKT/mTOR pathway. In functional experiments, peptide ARHGEF9 could suppress the protein expressions of p-PIK3K, p-AKT and p-mTOR, while IGF-1 could reverse this effect.
This study identifies 6 new prognostic biomarkers for glioma patients. Among them, peptide ARHGEF9 gene is an inhibitory gene functioning by targeting PI3K/AKT/mTOR pathway.
人类大脑神经系统中最常见的恶性肿瘤是神经胶质瘤。肽是由 - 氨基酸的肽键形成的化合物，多肽药物的发展已广泛应用于许多领域。我们计划研究神经胶质瘤中有临床价值的潜在肽。
基于公共数据库，我们针对神经胶质瘤差异表达基因（DEG）和与神经胶质瘤预后相关的肽基因之间的常见基因。然后，通过 LASSO-Cox 分析、预后风险模型和列线图对这些常见基因进行分析，以确定关键的预后肽基因和本研究中的靶基因。接下来，通过生物信息学分析和功能实验探索靶基因在神经胶质瘤中的作用机制。
我们总共获得了 26 个重叠基因用于进一步研究。之后，得到了 6 个独立的预后因素（REPIN1、PSD3、RDX、CDK4、FANCI 和 ARHGEF9），并应用于构建预后列线图，ARHGEF9 是本研究中的靶基因。接下来，发现肽 ARHGEF9 抑制神经胶质瘤细胞的发育。通过 Spearman 相关分析，ARHGEF9 与 PI3K/AKT/mTOR 通路密切相关。在功能实验中，肽 ARHGEF9 可以抑制 p-PIK3K、p-AKT 和 p-mTOR 的蛋白表达，而 IGF-1 可以逆转这种作用。
本研究确定了 6 个新的神经胶质瘤患者预后生物标志物。其中，肽 ARHGEF9 基因是一种通过靶向 PI3K/AKT/mTOR 通路发挥抑制作用的基因。
