title: Tumor type M2 pyruvate kinase (TuM2-PK) as a novel plasma tumor marker in melanoma.
abstract: Proliferating cells express the pyruvate kinase isoenzyme type M2 (M2-PK). This enzyme exists as an active tetramer and an inactive dimer. The dimeric form is predominantly found in tumor cells and is therefore termed Tumor M2-PK (TuM2-PK). TuM2-PK molecules are released into the peripheral blood and may hereby function as a marker of tumor load in cancer patients. Our study was aimed to investigate TuM2-PK as a potential plasma marker in melanoma patients compared to the well-established serum marker S100beta. We measured the concentration of TuM2-PK in plasma and S100beta in corresponding serum samples from 300 melanoma patients and 53 healthy controls using a sandwich ELISA and an immunoluminometric assay, respectively. Plasma concentrations of TuM2-PK were significantly increased in melanoma patients compared to healthy controls (9.30 U/ml vs. 7.20 U/ml; p = 0.0036) and correlated with tumor load (p < 0.0005) and disease stage (p < 0.0005). Patients with elevated plasma TuM2-PK (cut-off = 15 U/ml) presented a reduced overall (p < 0.000005) and progression-free (p = 0.023) survival. Multivariate analysis revealed plasma TuM2-PK and serum S100beta as independent predictors of overall survival in metastasized patients. Neither plasma TuM2-PK nor serum S100beta showed prognostic relevance for tumor-free patients. Although the sensitivity and specificity to predict disease progression or death was higher for serum S100beta compared to plasma TuM2-PK, the combination of both markers improved the estimation of prognosis compared to that of serum S100beta alone.
authors.affiliation: Skin Cancer Unit, German Cancer Research Center Heidelberg/Department of Dermatology, University Hospital Mannheim, Germany. s.ugurel@dkfz.de
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
authors.forename: Nellie
authors.initials: N
authors.lastname: Bell
authors.forename: Antje
authors.initials: A
authors.lastname: Sucker
authors.forename: Anette
authors.initials: A
authors.lastname: Zimpfer
authors.forename: Werner
authors.initials: W
authors.lastname: Rittgen
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology*; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood; D011770:Pyruvate Kinase / Q000097:blood*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D012878:Skin Neoplasms / Q000201:enzymology*
chemical_list: D014408:Biomarkers, Tumor; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D011770:Pyruvate Kinase