Expression of hypoxia‐inducible factor 1α, glucose transporter 1, and hexokinase 2 in primary central nervous system lymphoma and the correlation with the biological behaviors

• DOI: 10.1002/brb3.1718
• Publication Date: 2020-06-13T05:29:01Z
• Authors: Na Shen; Yaming Wang; Xuefei Sun; Xueyan Bai; Jinglan He; Qu Cui; Jun Qian; Hong Zhu; Yuedan Chen; Ruixian Xing; Qing Liu; Yuchen Wu; Junhong Li; Wenyuan Lai; Shengjun Sun; Nan Ji; Yuanbo Liu
• Keywords: Adult; Male; 0301 basic medicine; Lymphoma; Neurosciences. Biological psychiatry. Neuropsychiatry; Central Nervous System Neoplasms; 03 medical and health sciences; glucose transporter 1; Hexokinase; Biomarkers, Tumor; Tumor Microenvironment; Humans; Hypoxia; Original Research; Aged; Aged, 80 and over; Glucose Transporter Type 1; primary central nervous system lymphoma; prognostic factors; Middle Aged; Hypoxia-Inducible Factor 1, alpha Subunit; hexokinase 2; hypoxia‐inducible factor 1α; 3. Good health; Female; Glycolysis; RC321-571

AbstractBackgroundIt has been indicated that abnormal glucose metabolism mediated by hypoxia‐inducible factor 1α (HIF‐1α) played an essential role in the development of solid tumor. However, there were rare studies about the role of them in primary central nervous system lymphoma (PCNSL).ObjectiveTo investigate the protein levels of HIF‐1α, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in PCNSL and whether their levels are associated with prognostic factors.MethodsExpression of HIF‐1α, GLUT1, and HK2 in 39 tumor tissues was evaluated by immunohistochemical stainning. The correlation of the expression of HIF‐1α with the protein level of GLUT1 and HK2 was investigated. In addition, the association between these protein expression levels and clinical parameters and prognosis was analyzed.ResultsIn the tumor specimens of PCNSL, positive stainings of HIF‐1α, GLUT1, and HK2 were in 23 patients (58.97%), 25 patients (64.1%), and 26 patients (66.67%), respectively, which were associated with the expression level of lactic dehydrogenase (LDH), but not with age, gender, number of lesion, ECOG score, or deep structure. The expression of HIF‐1α was positively correlated with the expression of GLUT1 (p < .01, r = .749) and HK2 (p < .01, r = .787). Univariate analysis showed that upregulated GLUT1 was unfavorable predictors of progression‐free survival (PFS) in PCNSL. The results of Cox proportional hazards model showed GLUT1 was significantly associated with shorter PFS (hazard ration: 5.65; 95% confidence interval: 1.23–25.84; p = .026).ConclusionsThis study indicated that there was a hypoxic microenvironment and HIF‐1α was involved in the regulation of glycolysis pathway in PCNSL. GLUT1 might be a potential marker for shorter PFS in PCNSL.