Lower ratio of IMPDH1 to IMPDH2 sensitizes gliomas to chemotherapy

IF 4.8 3区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cancer gene therapy Pub Date : 2024-06-13 DOI:10.1038/s41417-024-00793-5

Xiaoyu Ruan, Yundong Xiong, Xiaoman Li, Ence Yang, Jiadong Wang

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Abstract

Gliomas are the most common primary tumors of the central nervous system, with approximately half of patients presenting with the most aggressive form of glioblastoma. Although several molecular markers for glioma have been identified, they are not sufficient to predict the prognosis due to the extensive genetic heterogeneity within glioma. Our study reveals that the ratio of IMPDH1 to IMPDH2 expression levels serves as a molecular indicator for glioma treatment prognosis. Patients with a higher IMPDH1/IMPDH2 ratio exhibit a worse prognosis, while those with a lower ratio display a more favorable prognosis. We further demonstrate that IMPDH1 plays a crucial role in maintaining cellular GTP/GDP levels following DNA damage compared to IMPDH2. In the absence of IMPDH1, cells experience an imbalance in the GTP/GDP ratio, impairing DNA damage repair capabilities and rendering them more sensitive to TMZ. This study not only introduces a novel prognostic indicator for glioma clinical diagnosis but also offers innovative insights for precise and stratified glioma treatment.

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较低的 IMPDH1 与 IMPDH2 比率会使胶质瘤对化疗敏感。

胶质瘤是中枢神经系统最常见的原发性肿瘤，约有一半的患者表现为最具侵袭性的胶质母细胞瘤。虽然胶质瘤的一些分子标记已被确定，但由于胶质瘤内部存在广泛的遗传异质性，这些标记不足以预测预后。我们的研究发现，IMPDH1与IMPDH2表达水平的比值可作为胶质瘤治疗预后的分子指标。IMPDH1/IMPDH2比值较高的患者预后较差，而比值较低的患者预后较好。我们进一步证明，与 IMPDH2 相比，IMPDH1 在 DNA 损伤后维持细胞 GTP/GDP 水平方面起着至关重要的作用。如果缺乏 IMPDH1，细胞的 GTP/GDP 比值就会失衡，从而损害 DNA 损伤修复能力，使细胞对 TMZ 更为敏感。这项研究不仅为胶质瘤的临床诊断提供了一个新的预后指标，还为胶质瘤的精确分层治疗提供了创新见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer gene therapy 医学-生物工程与应用微生物

CiteScore

10.20

自引率

0.00%

发文量

150

审稿时长

4-8 weeks

期刊介绍： Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair. Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.