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Abstract：
Parthanatos, a cell death mechanism triggered by PARP-1 activation, is implicated in oncogenic processes, yet their role in low-grade gliomas (LGG) remains poorly understood. This research investigates Parthanatos-related miRNAs\' prognostic and immunomodulatory potential, alongside their influence on therapeutic outcomes in LGGs. Comprehensive miRNA and mRNA profiles of LGG patients were extracted from TCGA and CGGA databases, integrating clinical parameters to identify Parthanatos-associated miRNAs. IHC data validated the expression levels of Parthanatos-related genes in glioma versus normal brain tissues. Protein-protein interaction networks and Spearman correlation analysis facilitated the identification of key miRNAs. Parthanatos-related miRNA indices (PMI) were screened using Lasso and assessed for their accuracy in predicting prognosis, comparing their associated potential molecular functions and heterogeneity of the immune microenvironment. Drug sensitivity was assessed between different groups and optimal therapeutic agents were predicted. Validate the expression levels of key miRNAs by qPCR. Ninety-one miRNAs significantly associated with Parthanatos were screened, through which a PMI prognosis model of nine miRNAs was constructed. The PMI score was able to independently predict the prognosis of patients with LGG, and the nomogram constructed based on the PMI provided a practical tool for clinical prediction of patient prognosis. The proportion of immune response was lower in patients in the high-risk group, and there were significant differences in drug sensitivity between different risk classes, while drugs such as Fasudil were identified as the most promising therapeutic agents for patients in the high-risk group. Our findings highlight the critical role of Parthanatos-associated miRNAs in the progression and treatment of LGG, offering novel insights into their prognostic value and therapeutic potential.
摘要：
Parthanatos,由PARP-1激活触发的细胞死亡机制，与致癌过程有关，然而，它们在低级别胶质瘤（LGG）中的作用仍然知之甚少。这项研究调查了Parthanatos相关的miRNA的预后和免疫调节潜力，以及它们对LGG治疗结果的影响。从TCGA和CGGA数据库中提取LGG患者的综合miRNA和mRNA谱，整合临床参数以鉴定Parthanatos相关miRNA。IHC数据验证了神经胶质瘤与正常脑组织中Parthanatos相关基因的表达水平。蛋白质-蛋白质相互作用网络和Spearman相关性分析促进了关键miRNA的鉴定。Parthanatos相关的miRNA指数（PMI）使用Lasso进行筛选，并评估其预测预后的准确性。比较它们相关的潜在分子功能和免疫微环境的异质性。评估不同组之间的药物敏感性，并预测最佳治疗药物。通过qPCR验证关键miRNA的表达水平。筛选了91个与Parthanatos显著相关的miRNAs，构建了9种miRNAs的PMI预后模型。PMI评分能够独立预测LGG患者的预后,基于PMI构建的列线图为临床预测患者预后提供了实用的工具。高风险组患者的免疫反应比例较低，不同风险类别之间的药物敏感性存在显着差异，而法舒地尔等药物被认为是高危患者最有希望的治疗药物。我们的发现强调了Parthanatos相关miRNAs在LGG的进展和治疗中的关键作用。提供对其预后价值和治疗潜力的新见解。
