Eilertsen Marte, Andersen Sigve, Al-Saad Samer, Kiselev Yury, Donnem Tom, Stenvold Helge, Pettersen Ingvild, Al-Shibli Khalid, Richardsen Elin, Busund Lill-Tove, Bremnes Roy M
Department of Clinical Medicine, University of Tromso, Tromso, Norway.
Department of Clinical Medicine, University of Tromso, Tromso, Norway; Department of Oncology, University Hospital of North Norway, Tromso, Norway.
PLoS One. 2014 Sep 16;9(9):e105038. doi: 10.1371/journal.pone.0105038. eCollection 2014.
Monocarboxylate transporters (MCTs) 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC.
Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4.
In univariate analyses; ↓ MCT1 (P = 0.021) and ↑ MCT4 (P = 0.027) expression in cancer cells, and ↑ MCT1 (P = 0.003), ↓ MCT2 (P = 0.006), ↓ MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001), ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001), ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031) and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016) were significant independent poor prognostic markers for DSS.
We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.
单羧酸转运蛋白(MCTs)1 - 4是乳酸转运蛋白,对癌细胞适应糖酵解上调至关重要。在此,我们旨在探讨它们对非小细胞肺癌(NSCLC)中癌细胞和肿瘤基质细胞疾病特异性生存(DSS)的预后影响。
构建组织微阵列(TMAs),其代表了335例未经选择的诊断为I - IIIA期NSCLC患者的癌组织和肿瘤基质组织。采用免疫组织化学法评估MCT1 - 4的表达。
在单因素分析中,癌细胞中MCT1表达降低(P = 0.021)和MCT4表达升高(P = 0.027),以及基质细胞中MCT1表达升高(P = 0.003)、MCT2表达降低(P = 0.006)、MCT3表达降低(P = 0.020)与不良DSS显著相关。在多因素分析中,癌细胞中MCT1表达降低(HR:1.9,95%CI:1.3 - 2.8,P = 0.001)、MCT2表达降低(HR:2.4,95%CI:1.5 - 3.9,P<0.001)、MCT3表达降低(HR:1.9,95%CI:1.1 - 3.5,P = 0.031)以及基质细胞中MCT1表达升高(HR:1.7,95%CI:1.1 - 2.7,P = 0.016)是DSS的显著独立不良预后标志物。
我们提供了关于MCT1作为NSCLC预后分层候选标志物的新信息。有趣的是,MCT1在癌细胞和基质细胞区室中显示出不同的、独立的预后影响。