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

Ling Lv,1 Xin Zhang,1 Yajun Liu,1 Xutong Zhu,2 Ruihan Pan,1 Lifa Huang1 1Department of Neurosurgery, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lifa Huang, Department of Neurosurgery, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), No. 54 Youdian Road, Hangzhou, 310006, People’s Republic of China, Tel/Fax +86-57186620251, Email jazzle@163.comPurpose: 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 f