title: Clinical use of p-proteasome in discriminating metastatic melanoma patients: comparative study with LDH, MIA and S100B protein.
abstract: Plasmatic proteasome (p-proteasome) has recently been described as a new marker for metastatic melanoma. The objective of this study was to compare the diagnostic and prognostic values of p-proteasome with three other melanoma serological markers: S100B protein, melanoma inhibitory activity protein (MIA) and lactate dehydrogenase (LDH) in the plasma of 121 stage I-IV melanoma patients. Laboratory analyses were performed by standardized ELISA (p-proteasome, MIA), immunoluminometric assay (S100B) and colorimetry (LDH). We found that all markers were relevant for discriminating metastatic from nonmetastatic patients but p-proteasome displayed the highest diagnostic accuracy. P-proteasome and S100B were the most sensitive (58.1%) and p-proteasome and MIA the most specific (98.7 and 100%) in detecting metastatic disease. P-proteasome and S100B had the highest area under receiver operating characteristics curve, 0.811 (95% CI: 0.725-0.897) and 0.822 (95% CI: 0.738-0.906), respectively. These two markers were the best in detecting patients with lymph node metastases. S100B, MIA and LDH diagnostic accuracy was increased when these markers were combined with p-proteasome. As shown with univariate analysis, shorter progression-free and overall survival rates were significantly associated with elevated plasma levels of each markers. The multivariate Cox regression analysis identified p-proteasome as the only independent predictor of a poorer progression-free survival (p = 0.030). In conclusion, this comparative study established that p-proteasome quantification in combination with other melanoma biomarkers is an attractive approach for the biological follow-up of melanoma patients.
authors.affiliation: Institute of Biomolecules Max Mousseron (IBMM), University Montpellier I and II, UMR CNRS 5247, Montpellier Cedex 5, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Henry
authors.forename: Cécile
authors.initials: C
authors.lastname: Fabre
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guiraud
authors.forename: Sophie
authors.initials: S
authors.lastname: Bastide
authors.forename: Pascale
authors.initials: P
authors.lastname: Fabbro-Peray
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.forename: Thierry
authors.initials: T
authors.lastname: Lavabre-Bertrand
authors.forename: Laurent
authors.initials: L
authors.lastname: Meunier
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Stoebner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D003124:Colorimetry; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000097:blood / Q000175:diagnosis* / Q000556:secondary; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D009367:Neoplasm Staging; D009414:Nerve Growth Factors / Q000097:blood*; D010949:Plasma; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D046988:Proteasome Endopeptidase Complex / Q000097:blood*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D012878:Skin Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D007770:L-Lactate Dehydrogenase; D046988:Proteasome Endopeptidase Complex