研究动态
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通过多组学数据库分析葡萄糖-6-磷酸脱氢酶(G6PD)与肺癌之间的相互联系。

Analysis of the interlink between glucose-6-phosphate dehydrogenase (G6PD) and lung cancer through multi-omics databases.

发表日期:2024 Aug 15
作者: Parth Thakor, M Quadir Siddiqui, Trushar R Patel
来源: Epigenetics & Chromatin

摘要:

6-磷酸葡萄糖脱氢酶 (G6PD) 是执行戊糖磷酸途径的关键酶。由于其在代谢网络中的关键节点位置,它与不同形式的癌症的发生和进展相关。尽管如此,其在肺癌中的功能作用和分子机制仍不清楚。本研究提供了与 G6PD 和肺癌相关的复杂信息。我们检索了各种公共数据集,包括 UALCAN、TCGA、cBioPortal 和 UCSC Xena 浏览器。获得的数据用于评估G6PD的表达、其临床特征、表观遗传调控、与肿瘤浸润的关系、肿瘤突变负荷、微卫星不稳定性、肿瘤微环境、免疫检查点基因、基因组改变和患者的总体生存率。本研究表明G6PD表达与肺癌的临床特征相关,包括疾病分期、种族、性别、年龄、吸烟习惯和淋巴结转移。此外,G6PD 的表达谱还通过调节 DNA 启动子甲基化活性来赋予表观遗传变化。启动子的甲基化会改变各种转录因子和基因的表达,从而影响免疫系统。这些事件与 G6PD 相关突变基因改变(FAM3A、LAG3、p53、KRAS)有关。整个情况影响患者的总体生存率和不良预后。使用 STRING、GO 和 KEGG 进行的功能研究发现,G6PD 主要参与标志性功能(代谢、免疫反应、增殖、凋亡、p53、HIF-1、FOXO、PI3K-AKT 信号传导)。这项工作提供了有关 G6PD 在肺癌中的功能的广泛知识,以及可能的预后治疗标志物的理论基础。© 2024 作者。
Glucose-6-Phosphate Dehydrogenase (G6PD) is a crucial enzyme that executes the pentose phosphate pathway. Due to its critical nodal position in the metabolic network, it is associated with different forms of cancer tumorigeneses and progression. Nonetheless, its functional role and molecular mechanism in lung cancer remain unknown. The present study provides intricate information associated with G6PD and Lung Cancer. Varieties of public datasets were retrieved by us, including UALCAN, TCGA, cBioPortal, and the UCSC Xena browser. The data obtained were used to assess the expression of G6PD, its clinical features, epigenetic regulation, relationship with tumour infiltration, tumour mutation burden, microsatellite instability, tumour microenvironment, immune checkpoint genes, genomic alteration, and patient's overall survival rate. The present study revealed that the G6PD expression was correlated with the clinical features of lung cancer including disease stage, race, sex, age, smoking habits, and lymph node metastasis. Moreover, the expression profile of G6PD also imparts epigenetic changes by modulating the DNA promoter methylation activity. Methylation of promoters changes the expression of various transcription factors, genes leading to an influence on the immune system. These events linked with G6PD-related mutational gene alterations (FAM3A, LAG3, p53, KRAS). The entire circumstance influences the patient's overall survival rate and poor prognosis. Functional investigation using STRING, GO, and KEGG found that G6PD primarily engages in hallmark functions (metabolism, immunological responses, proliferation, apoptosis, p53, HIF-1, FOXO, PI3K-AKT signaling). This work provides a wide knowledge of G6PD's function in lung cancer, as well as a theoretical foundation for possible prognostic therapeutic markers.© 2024 The Authors.