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通过多组学数据库分析葡萄糖-6-磷酸脱氢酶(G6PD)与肺癌之间的内在联系。

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

作者信息

Thakor Parth, Siddiqui M Quadir, Patel Trushar R

机构信息

Bapubhai Desaibhai Patel Institute of Paramedical Sciences, Charotar University of Science and Technology, CHARUSAT Campus, Changa, Gujarat, India.

Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, Lethbridge, AB, T1K 2E1, Canada.

出版信息

Heliyon. 2024 Jul 30;10(15):e35158. doi: 10.1016/j.heliyon.2024.e35158. eCollection 2024 Aug 15.

DOI:10.1016/j.heliyon.2024.e35158
PMID:39165939
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11334843/
Abstract

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.

摘要

葡萄糖-6-磷酸脱氢酶(G6PD)是一种执行磷酸戊糖途径的关键酶。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肿瘤发生和进展相关。然而,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和肺癌相关的详细信息。我们检索了各种公共数据集,包括UALCAN、TCGA、cBioPortal和UCSC Xena浏览器。所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、肿瘤突变负担、微卫星不稳定性、肿瘤微环境、免疫检查点基因、基因组改变以及患者的总生存率。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启动子甲基化活性引发表观遗传变化。启动子的甲基化改变了各种转录因子、基因的表达,从而对免疫系统产生影响。这些事件与G6PD相关的突变基因改变(FAM3A、LAG3、p53、KRAS)有关。整个情况影响患者的总生存率和预后不良。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)。这项工作提供了关于G6PD在肺癌中功能的广泛知识,以及可能的预后治疗标志物的理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d474/11334843/5c9340872dc4/gr7a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d474/11334843/5c9340872dc4/gr7a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d474/11334843/b1932207d040/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d474/11334843/8c1a17b56a13/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d474/11334843/3c289a3b3bd2/gr3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d474/11334843/236248b6e529/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d474/11334843/6819e6a4f997/gr5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d474/11334843/5c9340872dc4/gr7a.jpg

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