The expression of Hexokinase 2 and its hub genes are correlated with the prognosis in glioma.
The expression of Hexokinase 2 and its hub genes are correlated with the prognosis in glioma.
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己糖激酶2及其枢纽基因的表达与胶质瘤的预后相关
DOI：
10.1186/s12885-022-10001-y
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发表时间：
2022-08-18
期刊：
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
作者：
己糖激酶2（HK 2）是一种催化葡萄糖转化为葡萄糖-6-磷酸的酶，已发现其与恶性肿瘤生长相关。然而，HK 2的潜在免疫学和临床意义，特别是在神经胶质瘤患者的预后预测方面，尚未完全阐明。为了研究HK 2在胶质瘤患者中的表达、免疫学和临床意义，本研究使用了几个数据库，包括ONCOMINE、TIMER2.0、GEPIA、CGGA、UCSC、LinkedOmics、Metascape、STRING、GSCA和TISIDB，以及生化、细胞和病理学分析。此外，我们还对与HK 2正相关和负相关的hub基因进行了单变量、多变量考克斯回归和列线图分析，以探讨其在胶质瘤发生发展中的潜在调控机制。我们的研究结果表明，HK 2在大多数恶性肿瘤中高表达。HK 2在低级别胶质瘤（LGG）和胶质母细胞瘤（GBM）中的表达显著高于邻近正常组织。此外，HK 2表达与胶质瘤患者的临床参数、组织学表现和预后显著相关。具体而言，从UCSC Xena数据库分析下载的癌症基因组图谱的数据显示，HK 2的高表达与胶质瘤患者的不良预后密切相关。LinkedOmics数据库显示，HK 2相关基因主要富集于免疫相关细胞中。在LGG和GBM组织中，HK 2表达通常与公认的免疫检查点和多种免疫浸润物的丰度相关。类似地，Metascape数据库显示，HK 2相关基因主要在免疫相关通路和免疫细胞中富集和注释。进一步的研究还证实，抑制HK 2的表达显着抑制胶质瘤细胞的转移和血管生成拟态（VM）的形成，通过调节炎症和免疫调节因子的基因表达。HK 2的表达与胶质瘤的恶性性质密切相关，它通过激活多种免疫相关信号通路来调节免疫反应和免疫细胞的浸润。因此，HK 2及其hub基因可能成为胶质瘤治疗的潜在靶点。在线版本包含补充材料，可通过10.1186/s12885-022-10001-y获得。
Hexokinase 2 (HK2) is an enzyme that catalyses the conversion of glucose to glucose-6-phosphate, which has been found to be associated with malignant tumour growth. However, the potential immunological and clinical significance of HK2, especially in terms of prognostic prediction for patients with glioma, has not been fully elucidated. To investigate the expression, immunological and clinical significance of HK2 in patients with glioma, several databases, including ONCOMINE, TIMER2.0, GEPIA, CGGA, UCSC, LinkedOmics, Metascape, STRING, GSCA, and TISIDB, as well as biochemical, cellular, and pathological analyses, were used in this study. In addition, we performed univariate, multivariate Cox regression and nomogram analyses of the hub genes positively and negatively correlated with HK2 to explore the potential regulatory mechanism in the initiation and development of glioma. Our results demonstrated that HK2 was highly expressed in most malignant cancers. HK2 expression was significantly higher in lower grade glioma (LGG) and glioblastoma (GBM) than in adjacent normal tissue. In addition, HK2 expression was significantly correlated with clinical parameters, histological manifestations, and prognosis in glioma patients. Specifically, the data from The Cancer Genome Atlas downloaded from UCSC Xena database analysis showed that high expression of HK2 was strongly associated with poor prognosis in glioma patients. The LinkedOmics database indicated that HK2-related genes were mainly enriched in immune-related cells. In LGG and GBM tissues, HK2 expression is usually correlated with recognized immune checkpoints and the abundance of multiple immune infiltrates. Similarly, the Metascape database revealed that HK2-related genes were mainly enriched and annotated in immune-related pathways and immune cells. Further investigations also confirmed that the inhibition of HK2 expression remarkably suppressed metastasis and vasculogenic mimicry (VM) formation in glioma cells through regulating the gene expression of inflammatory and immune modulators. HK2 expression was closely associated with the malignant properties of glioma through activating multiple immune-related signalling pathways to regulate immune responses and the infiltration of immune cells. Thus, HK2 and its hub genes may be a potential target for the treatment of glioma. The online version contains supplementary material available at 10.1186/s12885-022-10001-y.
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