Immunohistochemical evaluation and prognostic value of monocarboxylate transporter 1 (MCT1) and 4 (MCT4) in T-cell non-Hodgkin lymphoma

细胞非霍奇金淋巴瘤中单羧酸转运蛋白 1 (MCT1) 和 4 (MCT4) 的免疫组织化学评估和预后价值

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作者:Hu Zhao, Yuan Chen, You-Ping Liao, Hai-Mei Chen, Qiu-Hong Yang, Yin Xiao, Jing Luo, Zhen-Zhen Chen, Lai Yi, Guo-Yu Hu

Abstract

Tumor cells often exhibit the Warburg effect, wherein, they preferentially undergo glycolysis over oxidative phosphorylation for energy production. Monocarboxylate transporter 1 (MCT1) and 4 (MCT4) are critical symporters mediating lactate efflux and preventing intracellular acidification during tumor growth. Numerous studies have focused on inhibiting MCT1 or MCT4 in various cancers. However, its role in T-cell lymphoma (TCL) is not yet investigated owing to the low incidence of TCL. This study was designed to investigate the expression of MCT1/MCT4 in patients with TCL and determine their prognostic value in this cancer. We performed immunohistochemistry to evaluate the expression level of MCT1/MCT4 in 38 TCL tissue samples and then compared their expression among different TCL subgroups, which were formed based on different clinical characteristics. Survival analysis was performed to evaluate the relationship between MCT1/MCT4 expression and both overall survival (OS) and progression-free survival (PFS). Our results revealed that MCT1 and MCT4 expression was significantly increased in TCL tissues compared to the control group. In addition, increased MCT1 expression associated with the female sex, advanced disease stage, increased serum LDH, Ki-67 at ≥ 50%, and intermediate or high-risk groups as categorized by the International Prognostic Index (IPI) score. We also found that increased MCT1 expression may be associated with reduced OS and PFS. In conclusion, MCT1 and MCT4 are overexpressed in patients with TCL and may predict poor prognosis. MCT1 inhibition might be a novel treatment strategy for TCL, and further preclinical trials are required.

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