Construction of a New Molecular Typing and Scoring System for Risk at S/G2 Phase between Different Prognostic Risks and Treatment Responsiveness in Low-Grade Gliomas

LIU Qiao; LIU Jie; FANG Jianing; GAN Xia; ZHOU Yongzhu; YU Xing; LIU Huai; WANG Hui

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Journal of Hunan Normal University(Medical Science) ›› 2025, Vol. 22 ›› Issue (6) : 29-45.

LIU Qiao^1,2, LIU Jie¹, FANG Jianing², GAN Xia², ZHOU Yongzhu¹, YU Xing¹, LIU Huai², WANG Hui²

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Abstract

Objective The major factors contributing to poor prognosis and treatment outcome in low grade glioma (LGG) include recurrence and malignant progression. Preventing cancer cells from prematurely entering the G2 stage from the S stage is crucial for tumor invasion and metastasis, and its molecular mechanisms still have research gaps in LGG. To investigate the predictive value of molecular isoforms based on risk crossing at S/G2 phase (RASG2) related genes on the prognosis and treatment responsiveness of LGG patients. Methods We downloaded data from 509 samples from the TCGA-LGG cohort, performed cluster analysis to identify different subtypes based on seven RASG2-related genes, and assessed subtype differences in clinicopathological and biological features. Estimation and single-sample gene set enrichment analyses were used to parse the tumor immune microenvironment (TIME) for LGG. A predictive scoring system was created using Cox regression analysis, Least Absolute Shrinkage with Selection Operator regression, and the Random Forest algorithm. This scoring system was used to categorize LGG patients into a high RASG2S (risk crossing at S/G2 phase score) group and a low RASG2S group. The association of RASG2S with the mutation status, prognosis, and treatment responsiveness of LGG patients was evaluated by mutation analysis, survival analysis, and drug sensitivity analysis based on the TCGA and CGGA cohorts. The differential expression of the RASG2 gene, centered on TICRR and MTBP, between LGG cells and normal cells, and its effect on the proliferation and invasive ability of LGG were verified by cellular experiments. Results All LGG patients were categorized into two subtypes, A and B, based on the expression profiles of seven RASG2-related genes. Patients with the two subtypes had distinct prognosis and TIME infiltration characteristics. Further constructed RASG2S independently predicted the prognosis and treatment responsiveness of LGG, and patients in the low RASG2S group had a significantly better prognosis, with a higher proportion of IDH mutations, 1p19q co-deletions, but with lower TIME immune cell infiltration, tumor mutational load and higher temozolomide sensitivity. Conclusion This study reveals a novel RASG2-associated gene signature that can be used to predict prognosis and treatment responsiveness in patients with LGG, which may contribute to clinical decision-making for precision treatment of LGG.

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low-grade glioma / risk crossing at S/G2 phase / prognosis / immunotherapy, temozolomide

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LIU Qiao, LIU Jie, FANG Jianing, GAN Xia, ZHOU Yongzhu, YU Xing, LIU Huai, WANG Hui. Construction of a New Molecular Typing and Scoring System for Risk at S/G2 Phase between Different Prognostic Risks and Treatment Responsiveness in Low-Grade Gliomas[J]. Journal of Hunan Normal University(Medical Science). 2025, 22(6): 29-45

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