16. Epstein-barr virus association Hexokinase 2 expression in Natural killer/t-cell lymphoma
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Abstract
Natural Killer/T cell lymphoma (NK/TL) is an aggressive type of cancer originated from the transformation of natural killer cells and T cells and is more typical in Asia. The common risk factor is Epstein-Barr virus (EBV), a member of the herpes virus family. Hexokinase 2 enzyme (HK2) expression has long been found to play a certain role in glycolysis and tumor proliferation in several cancers. Our study was conducted on 22 patients diagnosed with NK/TL to investigate the relationship between HK2 and EBV in cancer progression. HK2 expression was measured using the immunohistochemistry (IHC) technique; EBV status was determined using Realtime PCR. Our data showed 16 out of 22 research subjects (72.7%) were positive with HK2 expression. Our results showed a significant differencein EBV copy numbers in tumors between tumors not expressing HK2 and tumors expressing HK2 (p = 0.02). This can be a significant finding and suggests further research is required to understand the relationship and pathological mechanism of EBV and HK2 on NK/TL.
Article Details
Keywords
Hexokinase 2, Epstein-Barr virus, Natural Killer/T-cell Lymphoma
References
2. Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene. 2003; 22(33): 5108-5121. doi:10.1038/sj.onc.1206556.
3. Shannon-Lowe C, Rickinson AB, Bell AI. Epstein–Barr virus-associated lymphomas. Philos Trans R Soc B Biol Sci. 2017; 372(1732): 20160271. doi:10.1098/rstb.2016.0271.
4. Wang H, Fu BB, Gale RP, Liang Y. NK-/T-cell lymphomas. Leukemia. 2021; 35(9): 2460-2468. doi:10.1038/s41375-021-01313-2.
5. Wang W, Nong L, Liang L, et al. Extranodal NK/T-cell lymphoma, nasal type without evidence of EBV infection. Oncol Lett. 2020; 20(3): 2665-2676. doi:10.3892/ol.2020.11842.
6. Mathupala SP, Ko YH, Pedersen PL. Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene. 2006; 25(34): 4777-4786. doi:10.1038/sj.onc.1209603.
7. Roberts DJ, Miyamoto S. Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy. Cell Death Differ. 2015; 22(2): 248-257. doi:10.1038/cdd.2014.173.
8. Bhalla K, Jaber S, Nahid M N, et al. Role of hypoxia in Diffuse Large B-cell Lymphoma: Metabolic repression and selective translation of HK2 facilitates development of DLBCL. Sci Rep. 2018; 8(1): 744. doi:10.1038/s41598-018-19182-8.
9. Piccaluga PP, Weber A, Ambrosio MR, Ahmed Y, Leoncini L. Epstein–Barr Virus-Induced Metabolic Rearrangements in Human B-Cell Lymphomas. Front Microbiol. 2018; 9:1233. doi:10.3389/fmicb.2018.01233.
10. Young LS, Dawson CW, Eliopoulos AG. The expression and function of Epstein-Barr virus encoded latent genes. Mol Pathol. 2000; 53(5): 238-247.
11. Dawson CW, Port RJ, Young LS. The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Semin Cancer Biol. 2012; 22(2): 144-153. doi:10.1016/j.semcancer.2012.01.004.
12. Xiao L, Hu ZY, Dong X, et al. Targeting Epstein-Barr virus oncoprotein LMP1-mediated glycolysis sensitizes nasopharyngeal carcinoma to radiation therapy. Oncogene. 2014; 33(37): 4568-4578. doi:10.1038/onc.2014.32.
13. Fei Q, Tian XK, Wu J, et al. Prognostic significance of Epstein–Barr virus DNA in NK/T-cell lymphoma: a meta-analysis. OncoTargets Ther. 2018; 11:997-1004. doi:10.2147/OTT.S153942.
14. Lee J, Suh C, Huh J, et al. Effect of positive bone marrow EBV in situ hybridization in staging and survival of localized extranodal natural killer/T-cell lymphoma, nasal-type. Clin Cancer Res Off J Am Assoc Cancer Res. 2007; 13(11): 3250-3254. doi:10.1158/1078-0432.CCR-06-2373.
15. Liu C, Wang X, Zhang Y. The Roles of HK2 on Tumorigenesis of Cervical Cancer. Technol Cancer Res Treat. 2019; 18:1533033819871306. doi:10.1177/1533033819871306.
16. Wang H, Wang L, Zhang Y, Wang J, Deng Y, Lin D. Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth. Cancer Cell Int. 2016; 16(1): 9. doi:10.1186/s12935-016-0280-y.