Tong Ying-Hui, Hu Xiao-Ping, Xiang Xue-Ping, Fang Luo
Department of Pharmacy, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Department of Pharmacy, Zhejiang Provincial People's Hospital, Hangzhou, China.
Transl Cancer Res. 2021 Mar;10(3):1336-1345. doi: 10.21037/tcr-20-3117.
The monocarboxylate transporter (MCT) family especially MCT1 and MCT4 have been recognized to play an important role in lactate transport, a key glycolytic product. The expression of MCT1 and MCT4 expression was previously found to be related to poor outcome in various cancer types. In this study, we investigated the expression status of MCT1 and MCT4 and their relationship with prognosis in non-small cell lung cancer (NSCLC).
Expression of MCT4 and MCT1 in NSCLC tumor and adjacent lung tissues were detected by immunohistochemistry. Kaplan-Meier plots were used to evaluate two proteins' prognostic role, and the log-rank test obtained the P value. For multivariate analysis, the Cox proportional-hazards regression method was performed.
High MCT4 and MCT1 expression was observed in cancer cells, with a rate of 45% for MCT4 versus 15% for MCT1 among all NSCLC patients. High expression of MCT4, and not MCT1, was associated with worse overall survival (OS) [hazard ratio (HR) =1.96 (1.06-3.75), P=0.032] and progression-free survival (PFS) [HR =1.72 (1.05-2.93), P=0.032] in NSCLC patients. In our multivariate analysis, advanced cancer stage and high MCT4 level were identified as independent predictive indicators for both PFS [HR(MCT4) =1.888 (1.114-3.199), P=0.018 and OS [HR (MCT4) =2.421 (1.271-4.610), P=0.007]. Subgroup and interaction analyses were also performed in different clinical characteristic groups and no significant differences were observed.
High MCT4 expression is a predictive marker for worse outcome in NSCLC patients.
单羧酸转运体(MCT)家族尤其是MCT1和MCT4,已被认为在乳酸(一种关键的糖酵解产物)转运中发挥重要作用。先前发现MCT1和MCT4的表达与多种癌症类型的不良预后相关。在本研究中,我们调查了MCT1和MCT4的表达状态及其与非小细胞肺癌(NSCLC)预后的关系。
采用免疫组织化学法检测NSCLC肿瘤组织及癌旁肺组织中MCT4和MCT1的表达。用Kaplan-Meier曲线评估这两种蛋白的预后作用,通过对数秩检验获得P值。多因素分析采用Cox比例风险回归方法。
在癌细胞中观察到MCT4和MCT1高表达,在所有NSCLC患者中,MCT4的高表达率为45%,而MCT1为15%。MCT4而非MCT1的高表达与NSCLC患者较差的总生存期(OS)[风险比(HR)=1.96(1.06 - 3.75),P = 0.032]和无进展生存期(PFS)[HR = 1.72(1.05 - 2.93),P = 0.032]相关。在我们的多因素分析中,癌症晚期和高MCT4水平被确定为PFS[HR(MCT4)= 1.888(1.114 - 3.199),P = 0.018]和OS[HR(MCT4)= 2.421(1.271 - 4.610),P = 0.007]的独立预测指标。还在不同临床特征组中进行了亚组和相互作用分析,未观察到显著差异。
MCT4高表达是NSCLC患者预后较差的预测标志物。