Zhang Yi-Bin, Zheng Shu-Fa, Ma Lin-Jie, Lin Peng, Shang-Guan Huang-Cheng, Lin Yuan-Xiang, Kang De-Zhi, Yao Pei-Sen
Department of Neurosurgery, Neurosurgical Research Institute, First Affiliated Hospital, Fujian Medical University, Fuzhou 350004, China.
Department of Neurology and Neurosurgery, Changji Traditional Chinese Medicine Hospital, Changji 831100, China.
Brain Sci. 2022 Jul 30;12(8):1012. doi: 10.3390/brainsci12081012.
Objective Glioblastoma (GBM), a type of malignant glioma, is the most aggressive type of brain tumor and is associated with high mortality. Hexose-6-phosphate dehydrogenase (H6PD) has been detected in multiple tumors and is involved in tumor initiation and progression. However, the specific role and mechanism of H6PD in GBM remain unclear. Methods We performed pan-cancer analysis of expression and prognosis of H6PD in GBM using the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA). Subsequently, noncoding RNAs regulating H6PD expression were obtained by comprehensive analysis, including gene expression, prognosis, correlation, and immune infiltration. Finally, tumor immune infiltrates related to H6PD and survival were performed. Results Higher expression of H6PD was statistically significantly associated with an unfavorable outcome in GBM. Downregulation of hsa-miR-124-3p and hsa-miR-516b-5p in GBM was detected from GSE90603. Subsequently, OSMR-AS1 was observed in the regulation of H6PD via hsa-miR-516b-5p. Moreover, higher H6PD expression significantly correlated with immune infiltration of dendritic cells, immune checkpoint expression, and biomarkers of dendritic cells. Conclusions The OSMR-AS1/ miR-516b-5p axis was identified as the highest-potential upstream ncRNA-related pathway of H6PD in GBM. Furthermore, the present findings demonstrated that H6PD blockading might possess antitumor roles via regulating dendritic cell infiltration and immune checkpoint expression.
目的 胶质母细胞瘤（GBM）是一种恶性胶质瘤，是最具侵袭性的脑肿瘤类型，且死亡率高。已在多种肿瘤中检测到6-磷酸己糖脱氢酶（H6PD），其参与肿瘤的发生和进展。然而，H6PD在GBM中的具体作用和机制仍不清楚。方法 我们使用基因型-组织表达项目（GTEx）和癌症基因组图谱（TCGA）对GBM中H6PD的表达和预后进行了泛癌分析。随后，通过综合分析，包括基因表达、预后、相关性和免疫浸润，获得了调节H6PD表达的非编码RNA。最后，进行了与H6PD和生存相关的肿瘤免疫浸润分析。结果 H6PD的高表达在统计学上与GBM的不良预后显著相关。从GSE90603中检测到GBM中hsa-miR-124-3p和hsa-miR-516b-5p的下调。随后，观察到OSMR-AS1通过hsa-miR-516b-5p调节H6PD。此外，较高的H6PD表达与树突状细胞的免疫浸润、免疫检查点表达以及树突状细胞的生物标志物显著相关。结论 OSMR-AS1/miR-516b-5p轴被确定为GBM中H6PD最具潜力的上游非编码RNA相关途径。此外，本研究结果表明，H6PD阻断可能通过调节树突状细胞浸润和免疫检查点表达发挥抗肿瘤作用。
