Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
Genes (Basel). 2021 Aug 25;12(9):1305. doi: 10.3390/genes12091305.
In recent years, metabolic reprogramming has been identified as a hallmark of cancer. Accumulating evidence suggests that glutamine metabolism plays a crucial role in oncogenesis and the tumor microenvironment. In this study, we aimed to perform a systematic and comprehensive analysis of six key metabolic node genes involved in the dynamic regulation of glutamine metabolism (referred to as GLNM regulators) across 33 types of cancer.
We analyzed the gene expression, epigenetic regulation, and genomic alterations of six key GLNM regulators, including , , , , , and , in pan-cancer using several open-source platforms and databases. Additionally, we investigated the impacts of these gene expression changes on clinical outcomes, drug sensitivity, and the tumor microenvironment. We also attempted to investigate the upstream microRNA-mRNA molecular networks and the downstream signaling pathways involved in order to uncover the potential molecular mechanisms behind metabolic reprogramming.
We found that the expression levels of GLNM regulators varied across cancer types and were related to several genomic and immunological characteristics. While the immune scores were generally lower in the tumors with higher gene expression, the types of immune cell infiltration showed significantly different correlations among cancer types, dividing them into two clusters. Furthermore, we showed that elevated GLNM regulators expression was associated with poor overall survival in the majority of cancer types. Lastly, the expression of GLNM regulators was significantly associated with PD-L1 expression and drug sensitivity.
The elevated expression of GLNM regulators was associated with poorer cancer prognoses and a cold tumor microenvironment, providing novel insights into cancer treatment and possibly offering alternative options for the treatment of clinically refractory cancers.
近年来，代谢重编程已被确定为癌症的一个标志。越来越多的证据表明，谷氨酰胺代谢在肿瘤发生和肿瘤微环境中起着至关重要的作用。在这项研究中，我们旨在对涉及谷氨酰胺代谢动态调节的六个关键代谢节点基因（称为 GLNM 调节剂）在 33 种癌症中的表达进行系统和全面的分析。
我们使用几个开源平台和数据库分析了六个关键 GLNM 调节剂（包括 、 、 、 、 和 ）在泛癌中的基因表达、表观遗传调控和基因组改变。此外，我们研究了这些基因表达变化对临床结局、药物敏感性和肿瘤微环境的影响。我们还试图研究涉及的上游 microRNA-mRNA 分子网络和下游信号通路，以揭示代谢重编程背后的潜在分子机制。
我们发现 GLNM 调节剂的表达水平在癌症类型之间存在差异，与几种基因组和免疫学特征有关。虽然在基因表达较高的肿瘤中免疫评分通常较低，但免疫细胞浸润的类型在癌症类型之间表现出显著不同的相关性，将它们分为两个簇。此外，我们表明，GLNM 调节剂的高表达与大多数癌症类型的总体生存不良相关。最后，GLNM 调节剂的表达与 PD-L1 表达和药物敏感性显著相关。
GLNM 调节剂的表达上调与癌症预后不良和肿瘤微环境冷有关，为癌症治疗提供了新的见解，并可能为治疗临床上难治性癌症提供替代选择。
