Liu Tiantian, Qi Jianni, Wu Hao, Wang Le, Zhu Lihui, Qin Chengyong, Zhang Jiao, Zhu Qiang
Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, China.
Shandong Provincial Engineering and Technological Research Center for Liver Diseases Prevention and Control, Jinan, China.
Front Oncol. 2022 Oct 20;12:993503. doi: 10.3389/fonc.2022.993503. eCollection 2022.
Phosphogluconate dehydrogenase (PGD) is involved in the regulation of various tumors. However, its role in hepatocellular carcinoma (HCC) is poorly understood. This study tried to determine the prognostic efficacy of PGD and its value for immunotherapy in HCC.
The data from the TCGA database was used to explore the predictive power of PGD expression and methylation on the overall survival (OS) of HCC through Cox regression and the Kaplan-Meier analysis. Then, we used the GEO and ICGC database to further verify the predictive power. Finally, the relationship between PGD and immune cells and the relationship between PGD and the efficacy of immunotherapy were explored through bioinformatics analysis in HCC.
PGD is highly expressed in HCC tissues, which is negatively regulated by PGD methylation. Low PGD expression and PGD hypermethylation predict better OS in HCC patients. Besides, a meta-analysis based on the TCGA, GSE14520, and ICGC databases further confirms that low PGD expression is closely related to favorable OS. Then, we find significant differences of immune cell infiltrations between high and low PGD expression groups. Expressions of immune checkpoints, most HLA members and tumor mutation burden (TMB) are higher in the high PGD expression group, which indicates beneficial efficacy of immunotherapy in this group. And the potential mechanisms of PGD are exhibited.
PGD is an independent prognostic factor of HCC patients and plays an important role in immune cell infiltration and immunotherapy, which indicates that PGD can be used as a predictive biomarker for HCC immunotherapy.
6-磷酸葡萄糖酸脱氢酶（PGD）参与多种肿瘤的调控。然而，其在肝细胞癌（HCC）中的作用尚不清楚。本研究试图确定PGD在HCC中的预后效能及其对免疫治疗的价值。
利用来自TCGA数据库的数据，通过Cox回归和Kaplan-Meier分析，探讨PGD表达和甲基化对HCC患者总生存期（OS）的预测能力。然后，我们使用GEO和ICGC数据库进一步验证其预测能力。最后，通过生物信息学分析，探讨HCC中PGD与免疫细胞的关系以及PGD与免疫治疗疗效的关系。
PGD在HCC组织中高表达，其表达受PGD甲基化的负调控。低PGD表达和PGD高甲基化预示着HCC患者的OS较好。此外，基于TCGA、GSE14520和ICGC数据库的荟萃分析进一步证实，低PGD表达与良好的OS密切相关。然后，我们发现高、低PGD表达组之间免疫细胞浸润存在显著差异。高PGD表达组中免疫检查点、大多数HLA成员的表达以及肿瘤突变负荷（TMB）较高，这表明该组免疫治疗效果较好。并且展示了PGD的潜在机制。
PGD是HCC患者的独立预后因素，在免疫细胞浸润和免疫治疗中起重要作用，这表明PGD可作为HCC免疫治疗的预测生物标志物。
