PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer

Background: 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. Methods: 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. Results: 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. Conclusions: PKM2 expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy.