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Background: Hexokinase 2 not only plays a role in physiological function of human normal tissues and organs, but also plays a vital role in the process of glycolysis of tumor cells. However, there are few comprehensive studies on HK2 in esophageal carcinoma (ESCA) needs further study. Methods: Oncomine, Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used to analyze the expression differences of HK2 in Pan-cancer and ESCA cohort, and to analyze the correlation between HK2 expression level and clinicopathological features of TCGA ESCA samples. GO/KEGG, GGI, and PPI analysis of HK2 was performed using R software, LinkedOmics, GeneMANIA and STRING online tools. The correlation between HK2 and ESCA immune infiltration was analyzed TIMER and TCGA ESCA cohort. The correlation between HK2 expression level and m6A modification of ESCA was analyzed by utilizing TCGA ESCA cohort. Results: HK2 is highly expressed in a variety of tumors, and its high expression level in ESCA is closely related to the weight, cancer stages, tumor histology and tumor grade of ESCA. The analysis results of GO/KEGG showed that HK2 was closely related to cell adhesion molecule binding, cell-cell junction, ameboidal-type cell migration, insulin signaling pathway, hif-1 signaling pathway, and insulin resistance. GGI showed that HK2 associated genes were mainly involved in the glycolytic pathway. PPI showed that HK2 was closely related to HK1, GPI, and HK3, all of which played an important role in tumor proliferation. The analysis results of TIMER and TCGA ESCA cohort indicated that the HK2 expression level was related to the infiltration of various immune cells. TCGA ESCA cohort analyze indicated that the HK2 expression level was correlated with m6A modification genes. Conclusion: HK2 is associated with tumor immune infiltration and m6A modification of ESCA, and can be used as a potential biological target for diagnosis and therapy of ESCA.
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INTRODUCTION: Glioma is the most common type of the primary CNS tumor. Radiotherapy is an important treatment measure after surgery. However, its highly invasive character is the main reason of postoperative recurrence. The aim of the study was to probe the correlation between the invasion ability and the metabolite characteristics of glioma cells at the cellular level after irradiation by using 14.7T high-resolution nuclear proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: To determine the matrix metalloproteinase-2 (MMP-2) activity and metabolite ratios of glioma cells after irradiation with different doses of X-rays, U87 and C6 glioma cells were exposed to X-ray irradiation of 0, 1, 5, 10, and 15Gy. After 20h, the perchloric acid (PCA) extraction method was used to evaluate water-soluble metabolites [choline (Cho), creatine (Cr), and N-acetylaspartate (NAA)], and (1)H-MRS patterns and changes in metabolite ratios were observed in vitro by 14.7T high resolution (1)H-MRS. Matrigel invasion assays and gelatin zymography were performed to test the invasion ability of U87 and C6 glioma cells. RESULTS: Good MR spectra were obtained from PCA method extracts of U87 and C6 glioma cells. Both radiation-induced MMP-2 activity and the Cho/Cr and Cho/NAA ratios increased after irradiation, and their increase occurred in a dose-dependent manner. The MMP-2 activity and the Cho/Cr and Cho/NAA ratios of glioma cells increased after irradiation up to 10Gy and decreased thereafter. In particular, the Cho/NAA ratio of U87 cells increased from 3.55±0.06 (0Gy) to 9.13±0.30 (10Gy) and then declined to 5.94±0.15 (15Gy). Furthermore, the invasion ability of glioma cells had a strong positive correlation with the Cho/Cr and Cho/NAA ratios. Both the Cho/Cr ratio and the Cho/NAA ratio of U87 glioma cells were highly positively correlated with the number of invading cells in the Matrigel invasion assay. The Pearson's correlation coefficient (r) values of U87 cells were 0.89 (Cho/Cr ratio versus invasion ability) and 0.91 (Cho/NAA ratio versus invasion ability) (P<0.01). C6 cells exhibited similar changes to those of U87 cells. CONCLUSIONS: In vitro high-resolution (1)H-MRS is useful for detecting glioma invasiveness at the cellular level.
