Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, China.
Cell Biology Department, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
BMC Cancer. 2022 Aug 18;22(1):900. doi: 10.1186/s12885-022-10001-y.
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.
己糖激酶 2（HK2）是一种将葡萄糖转化为葡萄糖-6-磷酸的酶，已发现其与恶性肿瘤的生长有关。然而，HK2 的潜在免疫学和临床意义，特别是在预测胶质瘤患者的预后方面，尚未得到充分阐明。
为了研究 HK2 在胶质瘤患者中的表达、免疫学和临床意义，本研究使用了 ONCOMINE、TIMER2.0、GEPIA、CGGA、UCSC、LinkedOmics、Metascape、STRING、GSCA 和 TISIDB 等多个数据库，以及生化、细胞和病理分析。此外，我们对与 HK2 呈正相关和负相关的枢纽基因进行了单变量、多变量 Cox 回归和列线图分析，以探讨其在胶质瘤发生和发展中的潜在调控机制。
我们的结果表明，HK2 在大多数恶性肿瘤中高表达。在低级别胶质瘤（LGG）和胶质母细胞瘤（GBM）中，HK2 的表达明显高于邻近正常组织。此外，HK2 的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。具体来说，从 UCSC Xena 数据库下载的癌症基因组图谱（TCGA）数据分析表明，HK2 高表达与胶质瘤患者的预后不良密切相关。LinkedOmics 数据库表明，HK2 相关基因主要富集在免疫相关细胞中。在 LGG 和 GBM 组织中，HK2 的表达通常与公认的免疫检查点和多种免疫浸润细胞的丰度相关。同样，Metascape 数据库揭示，HK2 相关基因主要富集和注释在免疫相关通路和免疫细胞中。进一步的研究还证实，通过调节炎症和免疫调节剂的基因表达，抑制 HK2 的表达可显著抑制胶质瘤细胞的转移和血管生成模拟（VM）形成。
HK2 的表达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，与胶质瘤的恶性特征密切相关。因此，HK2 及其枢纽基因可能是治疗胶质瘤的潜在靶点。
