神经胶质瘤是一种常见的原发性中枢神经系统肿瘤，病理机制复杂。DNA损伤与修复（DDR）广泛参与通过修正和修复DNA损伤机制来调节细胞增殖和肿瘤发生。最近的研究报告了以下的肿瘤细胞在神经胶质瘤中的特性，包括DNA损伤的增加和降低的DNA修复能力。然而，在神经胶质瘤和DDR相关基因之间的关系尚不清楚。建立了DDR相关风险评分模型。通过Kaplan-Meier生存分析、肿瘤突变负荷（TMB）分析、免疫细胞浸润、治疗方案的敏感性等详细验证了该模型的有效性。此外，该模型的适应性经过了不同的神经胶质瘤数据集和不同的神经胶质瘤亚组的验证。为了进一步研究DDR相关基因（NUDT1）在神经胶质瘤中的分子机制，使用U251细胞进行敲除实验，然后进行MTT、创伤愈合和Transwell分析。得到了10个与预后相关的DDR相关签名基因，包括EID3、MGMT、YWHAG、PMS1、SHPRH、HUS1、NUDT1、GADD45G、APEX1和FAM175A。RT-qPCR结果表明，后五个基因在神经胶质瘤患者中高表达。有趣的是，高TMB得分患者有更长的生存期。在高风险评分组中，肿瘤微环境中免疫细胞浸润减少导致患者预后较差。治疗方案敏感性分析表明，低风险评分组对化疗更敏感。此外，风险评分模型对不同的神经胶质瘤数据集和不同的神经胶质瘤亚组具有良好的预测效果。体外机制研究显示，NUDT1敲除可减少肿瘤发生。此外，NUDT1的敲除显着降低了HIF-1α的表达水平。本研究建立的DDR相关风险评分模型对神经胶质瘤具有较好的预测性能。主要信息有：1.得到了10个与预后相关的DDR相关签名基因；2.在高风险评分组中，肿瘤微环境中的免疫细胞浸润减少导致患者预后较差；3.风险评分模型对不同的神经胶质瘤数据集和不同的神经胶质瘤亚组具有良好的预测效果；4.NUDT1敲除可减少神经胶质瘤的肿瘤发生，显着降低HIF-1α的表达水平。

Glioma is a common primary central nervous system tumor with complex pathogenesis. DNA damage and repair (DDR) is widely involved in regulating cell proliferation and tumorigenesis by correcting and repairing DNA damage mechanisms. Recent studies have reported the following properties in cancer cells in glioma, increased DNA damage and reduced DNA repair capacity. However, the relationship between glioma and DDR-related genes was unclear.DDR-related risk score model was built. The validity of this model was validated in detail through the Kaplan-Meier survival analysis, tumor mutational burden (TMB) analysis, immune cell infiltration, sensitivity to treatment regimens. Moreover, the model's adaptability was validated in different glioma data cohorts and different glioma subgroups. To further investigate the molecular mechanism of one of DDR-related gene (NUDT1) in glioma, U251 cell was used for the knockdown experiment, followed by MTT, wound healing and transwell analysis.Ten prognostic-related DDR-related signature genes were obtained, including EID3, MGMT, YWHAG, PMS1, SHPRH, HUS1, NUDT1, GADD45G, APEX1 and FAM175A. The RT-qPCR results suggested that the latter five genes were highly expressed in glioma patients. Interestingly, high TMB score had longer survival. In high-risk score groups, reduced immune cell infiltration in the tumor microenvironment lead to poorer patient outcomes. Sensitivity to treatment regimens analysis indicated that low-risk score groups were more sensitive to chemotherapeutics. Moreover, the risk score model had a good prediction effect on different glioma datasets and different glioma subgroups. In vitro mechanism study showed that knockdown of NUDT1 reduced tumorigenesis. Furthermore, knockdown of NUDT1 remarkably reduced the expression level of HIF-1α.DDR-related risk score model built-in this work has good predictive performance for glioma.Key messagesTen prognostic-related DDR-related signature genes were obtained, including EID3, MGMT, YWHAG, PMS1, SHPRH, HUS1, NUDT1, GADD45G, APEX1 and FAM175A.In high-risk score groups, reduced immune cell infiltration in the tumor microenvironment leads to poorer patient outcomes.The risk score model had a good prediction effect on different glioma datasets and different glioma subgroups.Knockdown of NUDT1 reduced tumorigenesis of glioma and remarkably reduced the expression level of HIF-1α.