PDF(Pubmed)
Abstract：
Mounting evidence has highlighted the multifunctional characteristics of glutamine metabolism (GM) in cancer initiation, progression and therapeutic regimens. However, the overall role of GM in the tumour microenvironment (TME), clinical stratification and therapeutic efficacy in patients with ovarian cancer (OC) has not been fully elucidated. Here, three distinct GM clusters were identified and exhibited different prognostic values, biological functions and immune infiltration in TME. Subsequently, glutamine metabolism prognostic index (GMPI) was constructed as a new scoring model to quantify the GM subtypes and was verified as an independent predictor of OC. Patients with low-GMPI exhibited favourable survival outcomes, lower enrichment of several oncogenic pathways, less immunosuppressive cell infiltration and better immunotherapy responses. Single-cell sequencing analysis revealed a unique evolutionary trajectory of OC cells from high-GMPI to low-GMPI, and OC cells with different GMPI might communicate with distinct cell populations through ligand-receptor interactions. Critically, the therapeutic efficacy of several drug candidates was validated based on patient-derived organoids (PDOs). The proposed GMPI could serve as a reliable signature for predicting patient prognosis and contribute to optimising therapeutic strategies for OC.
摘要：
越来越多的证据强调了谷氨酰胺代谢（GM）在癌症发生过程中的多功能特征，进展和治疗方案。然而,GM在肿瘤微环境(TME)中的总体作用，卵巢癌(OC)患者的临床分层和治疗效果尚未完全阐明.这里,确定了三个不同的GM聚类，并表现出不同的预后值，TME的生物学功能和免疫浸润。随后，谷氨酰胺代谢预后指数（GMPI）被构建为一种新的评分模型来量化GM亚型，并被验证为OC的独立预测因子。低GMPI患者表现出良好的生存结果，几种致癌途径的富集度较低，更少的免疫抑制细胞浸润和更好的免疫治疗反应。单细胞测序分析揭示了OC细胞从高GMPI到低GMPI的独特进化轨迹,具有不同GMPI的OC细胞可能通过配体-受体相互作用与不同的细胞群交流。严重的,根据患者来源的类器官(PDO)验证了几种候选药物的治疗效果.提出的GMPI可以作为预测患者预后的可靠标志，并有助于优化OC的治疗策略。
