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

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

作者信息

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

机构信息

XiangYa School of Medicine, Department of Hematology, Central South University, The Affiliated Zhuzhou Hospital, No.116 Changjiang South Road, Tianyuan District, Zhuzhou, Hunan, China.

出版信息

Clin Exp Med. 2023 Feb;23(1):55-64. doi: 10.1007/s10238-022-00805-4. Epub 2022 Mar 3.

DOI:10.1007/s10238-022-00805-4
PMID:35239073
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.

摘要

肿瘤细胞常常表现出瓦伯格效应,即它们在能量产生过程中优先进行糖酵解而非氧化磷酸化。单羧酸转运蛋白1(MCT1)和4(MCT4)是关键的同向转运体,在肿瘤生长过程中介导乳酸外流并防止细胞内酸化。许多研究都聚焦于在各种癌症中抑制MCT1或MCT4。然而,由于T细胞淋巴瘤(TCL)发病率较低,其在TCL中的作用尚未得到研究。本研究旨在调查TCL患者中MCT1/MCT4的表达情况,并确定它们在这种癌症中的预后价值。我们进行了免疫组织化学检测,以评估38例TCL组织样本中MCT1/MCT4的表达水平,然后比较它们在基于不同临床特征形成的不同TCL亚组中的表达情况。进行生存分析以评估MCT1/MCT4表达与总生存期(OS)和无进展生存期(PFS)之间的关系。我们的结果显示,与对照组相比,TCL组织中MCT1和MCT4的表达显著增加。此外,MCT1表达增加与女性、疾病晚期、血清乳酸脱氢酶升高、Ki-67≥50%以及国际预后指数(IPI)评分分类的中高危组相关。我们还发现,MCT1表达增加可能与OS和PFS降低有关。总之,MCT1和MCT4在TCL患者中过度表达,可能预示预后不良。抑制MCT1可能是TCL的一种新治疗策略,还需要进一步的临床前试验。

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