DataSheet_1_Pan-cancer analysis reveals that G6PD is a prognostic biomarker and therapeutic target for a variety of cancers.zip

BackgroundDespite 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.MethodsG6PD 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 in vitro 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.ResultsG6PD 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, in vitro functional validation showed that G6PD knockdown attenuated the phenotypes of proliferation in HCC.ConclusionG6PD may serve as a potential prognostic biomarker for cancers and may be a potential therapeutic target gene for tumor therapy.

尽管累积的证据显示葡萄糖-6-磷酸脱氢酶（G6PD）在众多肿瘤组织中高度表达，并在癌症的肿瘤发生和进展中发挥着显著作用，但关于G6PD的泛癌分析研究仍显不足。本研究旨在分析G6PD在泛癌中的表达状态及其预后意义。方法上，我们从多个数据资源中获取了G6PD表达数据，包括基因型-组织表达（Genotype-Tissue Expression）、癌症基因组图谱（The Cancer Genome Atlas）和肿瘤免疫估计资源（Tumor Immunity Estimation Resource），并利用这些数据评估了G6PD的表达、预后价值和临床特征。通过ESTIMATE算法分析了G6PD表达与免疫浸润细胞及肿瘤微环境之间的关联，并在泛癌范围内进行了功能富集分析。此外，利用包含403种药物的GDSC1数据库，探讨了药物敏感性水平与G6PD表达之间的关系。进一步地，我们还进行了临床验证和体外实验，以进一步验证G6PD在肝细胞癌（HCC）细胞中的角色及其与预后的相关性。统计分析和数据可视化使用R软件完成。结果显示，与正常组织相比，G6PD在大多数癌症中的表达上调。研究还发现，G6PD表达是预后指标，高水平的G6PD表达与多种癌症的较差临床预后相关，包括总生存期、疾病特异生存期和无进展生存期。此外，G6PD水平也与大多数癌症的免疫浸润相关，尤其是在KIRC、LGG和LIHC中。此外，G6PD表达与KIRP、BRCA、KIRC和LIHC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表明，G6PD参与代谢相关活动、免疫反应、增殖和凋亡。药物敏感性分析显示，大多数已识别的抗肿瘤药物的IC50值与G6PD表达呈正相关。值得注意的是，体外功能验证表明，G6PD敲低减弱了HCC细胞的增殖表型。结论上，G6PD可能作为癌症的潜在预后生物标志物，并可能成为肿瘤治疗的潜在治疗靶基因。