title: PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer.
abstract: 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.
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Papadaki
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Sfakianaki
authors.affiliation: Department of Pathology, University General Hospital of Heraklion, Heraklion, 71110 Crete, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Lagoudaki
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Giagkas
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Ioannidis
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Trypaki
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Tsakalaki
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Voutsina
authors.affiliation: Department of Pathology, University General Hospital of Heraklion, Heraklion, 71110 Crete, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Koutsopoulos
authors.affiliation: 1] Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece [2] Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, 71110 Crete, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.affiliation: 1] Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece [2] Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, 71110 Crete, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: 1] Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 71003 Crete, Greece [2] Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, 71110 Crete, Greece.
authors.forename: J
authors.initials: J
authors.lastname: Souglakos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D010984:Platinum / Q000008:administration & dosage; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D000093542:Gemcitabine; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D003841:Deoxycytidine; D000077143:Docetaxel; D005971:Glutamates; D006147:Guanine; D008565:Membrane Proteins; D000068437:Pemetrexed; D010984:Platinum; D012333:RNA, Messenger; D043823:Taxoids; D013963:Thyroid Hormones; D000093542:Gemcitabine; D000097810:Thyroid Hormone-Binding Proteins