Abstract
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.
Highlights
Recent studies show that Esophageal carcinoma (ESCA) ranks seventh in terms of incidence and sixth in mortality overall (Sung et al, 2021)
Oncomine database analysis showed that HK2 expression in bladder (Sanchez-Carbayo et al, 2006), brain and CNS (Bredel et al, 2005; French et al, 2005; Murat et al, 2008; Sun et al, 2006), esophageal (Hao et al, 2006), gastric (D’Errico et al, 2009), head and neck (Vasko et al, 2007), kidney (Jones et al, 2005; Gumz et al, 2007; Beroukhim et al, 2009), ovarian (Yoshihara et al, 2009), and pancreatic adenocarcinoma (Iacobuzio-Donahue et al, 2003; Badea et al, 2008; Pei et al, 2009) was higher than that in normal tissue samples
There are different data suggesting that HK2 may be highly expressed in both lymphoma (Piccaluga et al, 2007) and normal tissue samples (Storz et al, 2003), and it is speculated that this may be due to different sample sizes (Figure 1A)
Summary
Recent studies show that Esophageal carcinoma (ESCA) ranks seventh in terms of incidence and sixth in mortality overall (Sung et al, 2021). The occurrence and development of ESCA is an extremely complex biological process, and the expression of many genes has changed. Further research on the molecular mechanism of ESCA can provide new theoretical value for the diagnosis and treatment of tumors. HK2 plays a role in physiological function of human normal tissues and organs, and plays an important role in the glycolysis of tumor cells (Yu et al, 2021). Our previous study found that HK2 was highly expressed in ESCA, but no more studies were conducted on the biological function of HK2 (Liu et al, 2020b). Hexokinase 2 plays a role in physiological function of human normal tissues and organs, and plays a vital role in the process of glycolysis of tumor cells. There are few comprehensive studies on HK2 in esophageal carcinoma (ESCA) needs further study
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