泛癌分析表明，G6PD是多种癌症的预后生物标志物和治疗靶点。
Pan-cancer analysis reveals that G6PD is a prognostic biomarker and therapeutic target for a variety of cancers.
作者信息
Zeng Tao, Li Bin, Shu Xin, Pang Jiahui, Wang Heping, Cai Xianghao, Liao Yingying, Xiao Xiaolong, Chong Yutian, Gong Jiao, Li Xinhua
机构信息
Department of Infectious Diseases, Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Department of Infectious Diseases, The First People's Hospital of Kashi Prefecture, Kashi, China.
出版信息
Front Oncol. 2023 Aug 3;13:1183474. doi: 10.3389/fonc.2023.1183474. eCollection 2023.
BACKGROUND
Despite accumulating evidence revealing that Glucose-6-phosphate dehydrogenase (G6PD) is highly expressed in many tumor tissues and plays a remarkable role in cancer tumorigenesis and progression, there is still a lack of G6PD pan-cancer analysis. This study was designed to analyze the expression status and prognostic significance of G6PD in pan-cancer.
METHODS
G6PD expression data were obtained from multiple data resources including the Genotype-Tissue Expression, the Cancer Genome Atlas, and the Tumor Immunity Estimation Resource. These data were used to assess the G6PD expression, prognostic value, and clinical characteristics. The ESTIMATE algorithms were used to analyze the association between G6PD expression and immune-infiltrating cells and the tumor microenvironment. The functional enrichment analysis was also performed across pan-cancer. In addition, the GDSC1 database containing 403 drugs was utilized to explore the relationship between drug sensitivity and G6PD expression levels. Furthermore, we also performed clinical validation and experiments to further validate the role of G6PD in hepatocellular carcinoma (HCC) cells and its correlation with prognosis. The R software was used for statistical analysis and data visualization.
RESULTS
G6PD expression was upregulated in most cancers compared to their normal counterparts. The study also revealed that G6PD expression was a prognostic indicator and high levels of G6PD expression were correlated with worse clinical prognosis including overall survival, disease-specific survival, and progression-free interval in multiple cancers. Furthermore, the G6PD level was also related to cancer immunity infiltration in most of the cancers, especially in KIRC, LGG, and LIHC. In addition to this, G6PD expression was positively related to pathological stages of KIRP, BRCA, KIRC, and LIHC. Functional analysis and protein-protein interactions network results revealed that G6PD was involved in metabolism-related activities, immune responses, proliferation, and apoptosis. Drug sensitivity analysis showed that IC50 values of most identified anti-cancer drugs were positively correlated with the G6PD expression. Notably, functional validation showed that G6PD knockdown attenuated the phenotypes of proliferation in HCC.
CONCLUSION
G6PD may serve as a potential prognostic biomarker for cancers and may be a potential therapeutic target gene for tumor therapy.
背景
尽管越来越多的证据表明葡萄糖-6-磷酸脱氢酶（G6PD）在许多肿瘤组织中高表达，并在癌症的发生和发展中发挥着重要作用，但仍缺乏对G6PD的泛癌分析。本研究旨在分析G6PD在泛癌中的表达状态及其预后意义。
方法
从多个数据资源中获取G6PD表达数据，包括基因型-组织表达数据库、癌症基因组图谱和肿瘤免疫评估资源。这些数据用于评估G6PD的表达、预后价值和临床特征。使用ESTIMATE算法分析G6PD表达与免疫浸润细胞及肿瘤微环境之间的关联。还进行了泛癌的功能富集分析。此外，利用包含403种药物的GDSC1数据库探索药物敏感性与G6PD表达水平之间的关系。此外，我们还进行了临床验证和实验，以进一步验证G6PD在肝癌（HCC）细胞中的作用及其与预后的相关性。使用R软件进行统计分析和数据可视化。
结果
与正常组织相比，大多数癌症中G6PD表达上调。该研究还表明，G6PD表达是一种预后指标，在多种癌症中，高水平的G6PD表达与较差的临床预后相关，包括总生存期、疾病特异性生存期和无进展生存期。此外，在大多数癌症中，尤其是在肾透明细胞癌（KIRC）、低级别胶质瘤（LGG）和肝细胞癌（LIHC）中，G6PD水平也与癌症免疫浸润有关。除此之外，G6PD表达与肾乳头状癌（KIRP）、乳腺癌（BRCA）、肾透明细胞癌和肝细胞癌的病理分期呈正相关。功能分析和蛋白质-蛋白质相互作用网络结果显示，G6PD参与代谢相关活动、免疫反应、增殖和凋亡。药物敏感性分析表明，大多数已鉴定抗癌药物的半数抑制浓度（IC50）值与G6PD表达呈正相关。值得注意的是，功能验证表明，敲低G6PD可减弱肝癌细胞的增殖表型。
结论
G6PD可能作为癌症潜在的预后生物标志物，并且可能是肿瘤治疗的潜在治疗靶点基因。
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