目的:探讨胃癌化疗耐药形成机制中嘌呤代谢通路关键基因的作用及其调控机制,并评估其临床预测价值。方法:通过生物信息学分析筛选化疗耐药相关差异基因,结合功能富集分析确定嘌呤代谢通路的关键基因,并验证其表达水平及与患者预后的关系。同时,探索其可能的调控机制,并构建基于关键基因的预后模型。结果:化疗耐药组中嘌呤代谢通路活性显著增强,IMPDH2高表达且与胃癌患者较差预后相关。进一步分析提示c-Myc可能作为IMPDH2的上游转录因子,而KRAS通过MAPK通路上调c-Myc,推测存在c-Myc-IMPDH2-KRAS闭环调控机制。基于IMPDH2及相关基因构建的预后模型,能够有效预测胃癌患者的5年生存率和无病生存率。结论:本研究发现IMPDH2在胃癌化疗耐药中起关键作用,并推测其通过c-Myc-IMPDH2-KRAS闭环机制促进嘌呤代谢重编程及化疗耐药。构建的预后模型具有良好的预测能力,为胃癌精准治疗和个体化管理提供了新思路。Objective: To explore the role and regulatory mechanisms of key genes in the purine metabolism pathway involved in gastric cancer chemotherapy resistance and to evaluate their clinical prognostic value. Methods: Bioinformatics analysis was used to identify chemotherapy resistance-related differentially expressed genes. Functional enrichment analysis was performed to identify key genes in the purine metabolism pathway, followed by validation of their expression levels and association with patient prognosis. Potential regulatory mechanisms were explored, and a prognostic model based on the key genes was constructed. Results: The purine metabolism pathway was significantly upregulated in the chemotherapy-resistant group, with IMPDH2 highly expressed and associated with poor prognosis in gastric cancer patients. Further analysis suggested that c-Myc may act as the upstream transcription factor of IMPDH2, while KRAS may regulate c-Myc via the MAPK pathway, indicating the existence of a c-Myc-IMPDH2-KRAS feedback regulatory loop. A prognostic model based on IMPDH2 and related genes effectively predicted the 5-year overall survival and disease-free survival rates of gastric cancer patients. Conclusion: This study identified IMPDH2 as a key player in gastric cancer chemotherapy resistance and proposed that it may promote purine metabolism reprogramming and chemotherapy resistance via the c-Myc-IMPDH2-KRAS feedback loop. The constructed prognostic model demonstrated good predictive power, offering new insights for precision therapy and personalized management of gastr
本研究基于TCGA数据库,采用生物信息学方法构建了肾透明细胞癌(ccRCC)的蛋白质预后模型,并探讨了其免疫浸润特征。通过蛋白组学分析筛选出8个关键蛋白质,建立了预测患者预后的模型,并通过生存分析、ROC曲线及风险曲线对模型的稳定性与准确性进行了验证,进一步应用列线图预测患者的生存期,为临床决策提供辅助工具。此外,分析了模型中蛋白质间以及模型蛋白与其他关键蛋白之间的共表达关系,揭示了它们在ccRCC中的潜在作用。研究还深入探讨了免疫细胞的表达情况,并比较了高风险组与低风险组的免疫应答差异。结果显示,免疫细胞的浸润与患者预后密切相关,高风险组显示出较低的免疫应答,提示免疫微环境可能在肾透明细胞癌的进展中起重要作用。本研究为肾透明细胞癌的个体化治疗提供了新的预后模型,并为免疫治疗的相关研究奠定了基础。Based on the TCGA database, this study constructed a protein prognostic model for renal clear cell carcinoma using bioinformatics methods and explored its immune infiltration characteristics. Eight key proteins were identified through proteomic analysis, and a model for predicting patient prognosis was established. The stability and accuracy of the model were validated through survival analysis, ROC curve, and risk curve. Furthermore, column charts were used to predict patient survival, providing an auxiliary tool for clinical decision-making. In addition, the co expression relationships between proteins in the model and between model proteins and other key proteins were analyzed, revealing their potential roles in ccRCC. The study also delved into the expression of immune cells and compared the differences in immune responses between high-risk and low-risk groups. The results showed that the infiltration of immune cells is closely related to the prognosis of patients, and the high-risk group showed a lower immune response, suggesting that the immune microenvironment may play an important role in the progression of renal clear cell carcinoma. This study provides a new prognostic model for individualized treatment of renal clear cell carcinoma and lays the foundation for related research on immunotherapy.
胶质瘤相关癫痫(glioma-related epilepsy,GRE)是一种严重影响脑胶质瘤患者生活质量和治疗过程的并发症。肿瘤微环境中的基因和生物分子可能导致癫痫的机制和途径。此外,已经发现癫痫发作会促进脑肿瘤的生长,使得控制癫痫成为治疗脑肿瘤的关键因素。但在目前的认识中,并不是所有胶质瘤本身所携带的基因分子特征都参与GRE的发病机制。随着对GRE的认识不断加深,发现部分胶质瘤分子特征参与GRE的发病机制,其主要通过mTOR通路参与GRE的发生,这些通路同时也参与胶质瘤的致病过程。2021年世界卫生组织(World Health Organization,WHO)胶质瘤分类对弥漫性胶质瘤进行了新的分类,分为成人型和儿童型两大类,并进一步细分为星形细胞瘤、少突胶质细胞瘤和胶质母细胞瘤等类型。这一分类有助于更准确地理解和应用胶质瘤的分子特征,推动肿瘤病理诊断的规范化,并可能对GRE的治疗和预后评估产生影响。本综述通过最新WHO分类联系肿瘤微环境中的基因和生物分子,总结以往的研究和最近的发现,深入理解胶质瘤的特征及其与癫痫相关致病机制的关系,探寻更有效的治疗方法来抑制癫痫症状和肿瘤生长,对于改善GRE的诊断和治疗具有重要意义。
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