Papadaki C, Sfakianaki M, Lagoudaki E, Giagkas G, Ioannidis G, Trypaki M, Tsakalaki E, Voutsina A, Koutsopoulos A, Mavroudis D, Georgoulias V, Souglakos J
Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
Department of Pathology, University General Hospital of Heraklion, Heraklion, 71110 Crete, Greece.
Br J Cancer. 2014 Oct 28;111(9):1757-64. doi: 10.1038/bjc.2014.492. Epub 2014 Sep 18.
Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non-small-cell lung cancer (NSCLC) receiving platinum-based chemotherapy as first-line was investigated.
Quantitative real-time PCR was used to assess the expression of PKM2 in tumour samples from 148 and 157 NSCLC patients in the training and the validation set, respectively. All patients received front-line platinum-based chemotherapy. PKM2 mRNA expression was also analysed in a control group of 85 NSCLC patients treated with non-platinum containing regimens.
In the training set, high PKM2 mRNA levels were associated with decreased progression-free survival (PFS; 4.9 months vs 6.4, P=0.006), overall survival (OS; 10.1 vs 17.0 months, P=0.01) and disease control rate (DCR; 57.7% vs 74.3%; P=0.021) compared to patients with low PKM2 levels. In the validation set, high PKM2 mRNA levels were also associated with deceased PFS (3.7 vs 5.9 months, P=0.006), OS (8.3 vs 16.8 months, P=0.003) and DCR (57.7% vs 70.9%; P=0.049) compared to those with low PKM2 mRNA levels. There was no correlation between the PKM2 mRNA levels and the PFS (5.6 vs 5.9, P=0.43) or the OS (9.8 vs 10.1, P=0.51) in the control group. Multivariate analysis revealed high PKM2 mRNA expression as an independent predictive factor for the poor patients' outcome.
PKM2 expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy.
肿瘤细胞仅表达丙酮酸激酶（PKM2）的胚胎型M2亚型。PKM2的表达水平与铂类化合物在癌细胞系和异种移植模型中的作用相关。本研究探讨了PKM2在接受铂类化疗作为一线治疗的转移性/晚期非小细胞肺癌（NSCLC）患者中的潜在预测作用。
分别采用定量实时PCR检测训练集和验证集中148例和157例NSCLC患者肿瘤样本中PKM2的表达。所有患者均接受一线铂类化疗。同时对85例接受不含铂方案治疗的NSCLC患者作为对照组进行PKM2 mRNA表达分析。
在训练集中，与低PKM2水平的患者相比，高PKM2 mRNA水平与无进展生存期（PFS；4.9个月对6.4个月，P = 0.006）、总生存期（OS；10.1个月对17.0个月，P = 0.01）和疾病控制率（DCR；57.7%对74.3%；P = 0.021）降低相关。在验证集中，与低PKM2 mRNA水平患者相比，高PKM2 mRNA水平也与PFS降低（3.7个月对5.9个月，P = 0.006）、OS降低（8.3个月对16.8个月，P = 0.003）和DCR降低（57.7%对70.9%；P = 0.049）相关。在对照组中，PKM2 mRNA水平与PFS（5.6对5.9，P = 0.43）或OS（9.8对10.1，P = 0.51）无相关性。多因素分析显示高PKM2 mRNA表达是患者预后不良的独立预测因素。
PKM2表达可能是接受铂类化疗的晚期NSCLC患者铂敏感性的预测生物标志物。
