Ruan Yushu, Zeng Fanjun, Cheng Zhiqiang, Zhao Xianda, Fu Pin, Chen Honglei
Department of Respiratory Medicine, First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei 443003, P.R. China.
Department of Pathology, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China.
Oncol Lett. 2017 Nov;14(5):5727-5734. doi: 10.3892/ol.2017.6964. Epub 2017 Sep 15.
Monocarboxylate transporter 4 (MCT-4) serves a key function in transporting lactate across the plasma membrane in various types of human cancer. Evidence indicates that MCT-4 expression is associated with non-small cell lung cancer; however, the distribution and clinical significance of MCT-4 in the lung adenocarcinoma (AC) subtype remain unknown. Thus, the aim of the present study was to explore the clinicopathological significance and prognostic values of MCT-4 expression in lung AC. Quantum dots-based immunofluorescence histochemistry was performed to observe the expression of MCT-4 in 146 specimens of lung AC and corresponding normal lung tissues. MCT-4 protein and mRNA were detected by western blotting and reverse transcription-quantitative polymerase chain reaction from 30 fresh samples of lung AC and corresponding normal lung tissues. Of the 146 samples, 25 (17.1%) exhibited high and 121 (82.9%) exhibited low MCT-4 expression. MCT-4, at the protein and mRNA level, was significantly increased in tumor specimens compared with corresponding normal lung tissue (P<0.05). MCT-4 protein expression was significantly associated with depth of invasion (P=0.034). A survival curve analysis indicated that high MCT-4 expression in lung AC was associated with a decreased overall survival rate (P=0.001). Multivariate analysis demonstrated that high MCT-4 level was an independent prognostic factor (hazard ratio, 3.192; 95% confidence interval, 1.804-5.646; P=0.001) for patients with lung AC. The results have demonstrated that high MCT-4 expression is significantly associated with the poor prognosis and disease progression of patients with lung AC. Therefore, MCT-4 may be a candidate therapeutic target in lung AC.
单羧酸转运蛋白4(MCT - 4)在多种人类癌症中,对于乳酸跨质膜转运起着关键作用。有证据表明,MCT - 4的表达与非小细胞肺癌相关;然而,MCT - 4在肺腺癌(AC)亚型中的分布及临床意义仍不清楚。因此,本研究的目的是探讨MCT - 4在肺AC中的临床病理意义及预后价值。采用基于量子点的免疫荧光组织化学方法,观察146例肺AC标本及相应正常肺组织中MCT - 4的表达情况。通过蛋白质印迹法和逆转录 - 定量聚合酶链反应,检测30例新鲜肺AC标本及相应正常肺组织中的MCT - 4蛋白和mRNA。在146个样本中,25个(17.1%)呈现高MCT - 4表达,121个(82.9%)呈现低MCT - 4表达。与相应正常肺组织相比,肿瘤标本中MCT - 4在蛋白质和mRNA水平均显著升高(P<0.05)。MCT - 4蛋白表达与浸润深度显著相关(P = 0.034)。生存曲线分析表明,肺AC中高MCT - 4表达与总生存率降低相关(P = 0.001)。多因素分析显示,高MCT - 4水平是肺AC患者的独立预后因素(风险比,3.192;95%置信区间,1.804 - 5.646;P = 0.001)。结果表明,高MCT - 4表达与肺AC患者的不良预后及疾病进展显著相关。因此,MCT - 4可能是肺AC的一个候选治疗靶点。