Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer.

Q2 Medicine

BMC Clinical Pathology Pub Date : 2017-12-28 eCollection Date: 2017-01-01 DOI:10.1186/s12907-017-0067-7

Ayşe Latif, Amy L Chadwick, Sarah J Kitson, Hannah J Gregson, Vanitha N Sivalingam, James Bolton, Rhona J McVey, Stephen A Roberts, Kay M Marshall, Kaye J Williams, Ian J Stratford, Emma J Crosbie

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Abstract

Background: Endometrial cancer (EC) is a major health concern due to its rising incidence. Whilst early stage disease is generally cured by surgery, advanced EC has a poor prognosis with limited treatment options. Altered energy metabolism is a hallmark of malignancy. Cancer cells drive tumour growth through aerobic glycolysis and must export lactate to maintain intracellular pH. The aim of this study was to evaluate the expression of the lactate/proton monocarboxylate transporters MCT1 and MCT4 and their chaperone CD147 in EC, with the ultimate aim of directing future drug development.

Methods: MCT1, MCT4 and CD147 expression was examined using immunohistochemical analysis in 90 endometrial tumours and correlated with clinico-pathological characteristics and survival outcomes.

Results: MCT1 and MCT4 expression was observed in the cytoplasm, the plasma membrane or both locations. CD147 was detected in the plasma membrane and associated with MCT1 (p = 0.003) but not with MCT4 (p = 0.207) expression. High MCT1 expression was associated with reduced overall survival (p = 0.029) and remained statistically significant after adjustment for survival covariates (p = 0.017).

Conclusion: Our data suggest that MCT1 expression is an important marker of poor prognosis in EC. MCT1 inhibition may have potential as a treatment for advanced or recurrent EC.

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单羧酸盐转运体 1（MCT1）是子宫内膜癌独立的预后生物标志物。

背景：子宫内膜癌（EC）的发病率不断上升，已成为人们关注的主要健康问题。虽然早期疾病一般可通过手术治愈，但晚期子宫内膜癌的预后较差，治疗方案有限。能量代谢改变是恶性肿瘤的标志。癌细胞通过有氧糖酵解驱动肿瘤生长，并必须输出乳酸以维持细胞内的 pH 值。本研究旨在评估乳酸/质子一羧酸盐转运体MCT1和MCT4及其伴侣CD147在EC中的表达，最终目的是指导未来的药物开发：方法：采用免疫组化分析方法检测90例子宫内膜肿瘤中MCT1、MCT4和CD147的表达情况，并将其与临床病理特征和生存结果相关联：结果：观察到MCT1和MCT4在细胞质、质膜或两个位置均有表达。在质膜上检测到 CD147，它与 MCT1（p = 0.003）的表达有关，但与 MCT4（p = 0.207）的表达无关。MCT1的高表达与总生存率降低有关（p = 0.029），在调整生存协变量后仍具有统计学意义（p = 0.017）：我们的数据表明，MCT1表达是EC预后不良的重要标志。结论：我们的数据表明，MCT1表达是EC预后不良的重要标志物，抑制MCT1可能具有治疗晚期或复发性EC的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Clinical Pathology Medicine-Pathology and Forensic Medicine

CiteScore

3.30

自引率

0.00%

发文量

期刊介绍： BMC Clinical Pathology is an open access journal publishing original peer-reviewed research articles in all aspects of histopathology, haematology, clinical biochemistry, and medical microbiology (including virology, parasitology, and infection control). BMC Clinical Pathology (ISSN 1472-6890) is indexed/tracked/covered by PubMed, CAS, EMBASE, Scopus and Google Scholar.