目的：基于GINS家族成员在胶质瘤组织中表达水平对其分型，探究此分型预测胶质瘤患者的预后、免疫治疗疗效的有效性，采用TCMOI数据库虚拟筛选可靶向GINS的中药小分子。方法：数据库分析GINS基因组学、胶质瘤组织中差异表达基因与患者预后的关系，基于GINS家族成员基因表达对胶质瘤进行分型并分析各亚型的预后情况，数据库数据分析各亚型中的基因突变、基因富集、肿瘤纯度和免疫细胞浸润评分，以及与GINS2可能相互作用的中药小分子，最后用qPCR法检测中国人胶质瘤组织中GINS1~4 mRNA的表达水平以验证其与数据库数据的一致性。结果：GINS家族各成员间的基因、蛋白结构和功能相似，胶质瘤组织中GINS 家族成员呈高表达且与患者不良预后密切相关（P<0.05），基于GINS 家族成员在胶质瘤组织中表达水平的S1、S2 亚型分类能较好地预测胶质瘤患者的预后，S1 亚型主要突变基因为CDKN2A/B、EGFR、PTEN 而S2 亚型的突变基因为IDH1、TP53和ATRX，GINS家族可能通过调控免疫微环境影响胶质瘤患者预后，CD276 和CX3CL1可能是S1亚型胶质瘤患者实施免疫治疗的潜在靶点，CHEMBL66033、266935、293914、436859、1594881可能是潜在的靶向GINS2的中药小分子。结论：基于GINS 家族构建的胶质瘤分子分型有助于识别更适合免疫治疗的高风险患者，筛选出的中药小分子可为胶质瘤患者分子靶向治疗和免疫治疗提供参考。

Objective: The classification of GINS family members based on their expression level in glioma tissue was explored to predict the prognosis of glioma patients, the efficacy of immunotherapy and the small molecules of traditional Chinese medicine. Methods: The database analyzed the relationship between GINS genomics, differentially expressed genes in glioma tissue and patient prognosis. Classification of gliomas based on gene expression of GINS family members and analysis of the prognosis of each subtype. Database data was analyzed for mutations, gene enrichment, tumor purity and immune cell infiltration scores for each subtype, as well as for Chinese traditional medicine small molecules that may interact with GINS2. Finally, the expression levels of GINS1~4 mRNA in Chinese human glioma tissues were detected by qPCR to verify their consistency with the database data. Results: GINS family members share similarities in gene, protein structure and function. Furthermore, they are highly expressed in glioma tissues and are strongly associated with poor patient prognosis (P<0.05). The classification of S1 and S2 subtypes based on the expression level of GINS family members in glioma tissue can better predict the prognosis of glioma patients. The main mutant genes of the S1 subtype are CDKN2A/B, EGFR and PTEN, while the mutant genes of the S2 subtype are IDH1, TP53 and ATRX. In addition, GINS family may affect the prognosis of glioma patients by regulating the immune microenvironment. CD276, and CX3CL1 may be potential targets for immunotherapy in patients with S1 subtype glioma. CHEMBL66033, 266935, 293914, 436859 and 1594881 May be the potential Chinese medicine small molecules targeting GINS2. Conclusion: The molecular typing of glioma constructed based on GINS family helps identify high-risk patients more suitable for immunotherapy, and the selected traditional Chinese medicine small molecules can provide a reference for molecular targeted therapy and immunotherapy for glioma patients.

湖南省自然科学基金（No. 2023JJ30425）；湖南省卫生健康委科研课题（No. 202103011683）