Identification of PAICS as a Purine Metabolism-Based Prognostic Biomarker in Glioma and Functional Validation of its Targeting Native Inhibitors

FAN Ye; ZOU Heqin; JIANG Yiqun; ZHOU Weiping

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Journal of Hunan Normal University(Medical Science) ›› 2026, Vol. 23 ›› Issue (1) : 16-24.

Identification of PAICS as a Purine Metabolism-Based Prognostic Biomarker in Glioma and Functional Validation of its Targeting Native Inhibitors

FAN Ye^1,2, ZOU Heqin², JIANG Yiqun¹, ZHOU Weiping²

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Abstract

Objective A systematic evaluation of the clinical significance of purine metabolism-related genes in glioma, identification of key therapeutic targets, and validation of the antitumor potential of natural small-molecule inhibitors in combination with temozolomide. Methods Based on public databases, differentially expressed purine metabolism-related genes in glioma were identified. A prognostic prediction model was constructed and validated using machine learning algorithms, leading to the identification of key candidate genes. Molecular docking was employed to screen and identify natural inhibitors targeting PAICS. The inhibitory effects of these compounds on PAICS expression and cell proliferation were evaluated through in vitro experiments, and their synergistic efficacy with temozolomide was further assessed. Results Core purine metabolism-related genes were successfully identified, and the constructed prognostic model demonstrated robust discriminative performance in an independent cohort. PAICS was identified as a key gene, with vindoline and triptolide recognized through molecular docking as potential PAICS inhibitors. Cellular experiments revealed that both natural compounds downregulated PAICS expression and significantly suppressed glioma cell proliferation, with enhanced antiproliferative effects observed when combined with temozolomide. Conclusion PAICS serves as a potential prognostic biomarker and therapeutic target in glioma. Vindoline and triptolide enhance the antiproliferative effect of temozolomide by targeting PAICS, providing a novel strategic basis for combination therapy in glioma.

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glioma / PAICS / inhibitors / combination therapy

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FAN Ye, ZOU Heqin, JIANG Yiqun, ZHOU Weiping. Identification of PAICS as a Purine Metabolism-Based Prognostic Biomarker in Glioma and Functional Validation of its Targeting Native Inhibitors[J]. Journal of Hunan Normal University(Medical Science). 2026, 23(1): 16-24

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