Three Liquid-Liquid Phase Separation-Related Genes Associated with Prognosis in Glioma

Pharmacogenomics and Personalized Medicine Pub Date : 2024-04-22 DOI:10.2147/pgpm.s442000

Ling Lv, Xin Zhang, Yajun Liu, Xutong Zhu, Ruihan Pan, Lifa Huang

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Abstract

Purpose: Dysregulated liquid-liquid phase separation (LLPS) instigates tumorigenesis through biomolecular condensate dysfunction. However, the association between LLPS-associated genes and glioma remains underexplored.
Patients and Methods: Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR.
Results: A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature (TAGLN2, NTNG2, and IGF2BP2) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells.
Conclusion: This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients.

Keywords: liquid-liquid phase separation, glioma, prognostic model, molecular subtype, immune cell infiltration

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与胶质瘤预后相关的三个液-液相分离基因

目的：失调的液-液相分离（LLPS）会通过生物分子凝结物的功能障碍诱发肿瘤。然而，LLPS相关基因与胶质瘤之间的关联仍未得到充分探索：胶质瘤的差异表达基因（DEGs）来自 GSE50161 数据集，其中包括 34 个胶质瘤样本和 13 个正常样本。我们从公共数据库中分析了胶质瘤中LLPS相关的差异表达基因。这些基因为TCGA-胶质瘤数据集的分子亚型细化提供了依据。CIBERSORT评估了三个亚群的免疫细胞浸润情况。通过对交叉基因进行单变量和套索考克斯回归，设计出了一个预后模型。通过 RT-qPCR 验证了胶质瘤细胞中预后基因的表达：结果：在胶质瘤中总共发现了 673 个差异表达的 LLPS 相关基因。胶质瘤有三种不同的分子亚型（C1、C2 和 C3），免疫检查点基因 PD1 和 PDL1 的表达存在明显差异。不同亚型的免疫细胞浸润也存在差异。此外，还得出了一个三基因预后特征（TAGLN2、NTNG2 和 IGF2BP2），高危组和低危组之间存在显著的生存差异。在训练集和验证集中，预后模型的 1 年、3 年和 5 年生存率的 AUC 值都令人印象深刻。进一步分析显示，胶质瘤样本中的三个预后基因与免疫细胞之间存在明显的相关性。此外，我们还发现在胶质瘤肿瘤和细胞中，TAGLN2 和 IGF2BP2 上调，NTNG2 下调：本研究创新性地发现了LLPS相关基因在胶质瘤肿瘤分级和预后中的重要作用。构建的三基因预后模型有望加强胶质瘤患者的个性化预后评估并优化免疫治疗策略。关键词：液-液相分离；胶质瘤；预后模型；分子亚型；免疫细胞浸润

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Pharmacogenomics and Personalized Medicine

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