title: Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma.
abstract: BACKGROUND
  Soluble mesothelin (SM), megakaryocyte potentiating factor (MPF), and osteopontin (OPN) are blood biomarkers of mesothelioma. This study evaluates their use as markers of response to therapy and outcome.
  
  
  METHODS
  Sixty-two patients with malignant pleural mesothelioma were included in an observational multicenter study. Blood samples and matched computed tomography scans were collected at diagnosis and, when possible, during and after therapy. For each patient, the best overall radiological response was compared with the changes in serum SM, MPF, and plasma OPN levels across corresponding time points.
  
  
  RESULTS
  In five patients, blood sampling was done shortly before and after extrapleural pneumonectomy. SM and MPF levels markedly decreased after surgery, whereas OPN levels showed a median increase. Fifty-seven patients were surveilled during (and after) chemotherapy, of whom 27 (47%) had stable disease, 14 (25%) partial response, and 16 (28%) progressive disease. In patients with stable disease, SM and MPF levels did not change significantly across the corresponding time points, whereas OPN levels significantly decreased. In those with partial response, SM and MPF levels significantly decreased, whereas OPN levels showed no significant change. In patients with progressive disease, all three biomarker levels significantly increased. Patient responses correlated with a 15% change in all three biomarkers, although SM and MPF appeared more accurate than OPN. Low baseline OPN levels were independently associated with favorable progression-free survival and overall survival. Neither SM nor MPF showed prognostic value.
  
  
  CONCLUSIONS
  SM and MPF levels were more closely associated with disease course than OPN and might prove useful in monitoring patient response in mesothelioma. Baseline OPN levels were an independent negative predictor of survival. These promising results require further validation.
authors.affiliation: Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. kevin.hollevoet@gmail.com
authors.forename: Kevin
authors.initials: K
authors.lastname: Hollevoet
authors.forename: Kristiaan
authors.initials: K
authors.lastname: Nackaerts
authors.forename: Robert
authors.initials: R
authors.lastname: Gosselin
authors.forename: Walter
authors.initials: W
authors.lastname: De Wever
authors.forename: Lionel
authors.initials: L
authors.lastname: Bosquée
authors.forename: Paul
authors.initials: P
authors.lastname: De Vuyst
authors.forename: Paul
authors.initials: P
authors.lastname: Germonpré
authors.forename: Eliane
authors.initials: E
authors.lastname: Kellen
authors.forename: Catherine
authors.initials: C
authors.lastname: Legrand
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kishi
authors.forename: Joris R
authors.initials: JR
authors.lastname: Delanghe
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Meerbeeck
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins / Q000097:blood*; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood* / Q000401:mortality / Q000628:therapy; D008875:Middle Aged; D009367:Neoplasm Staging; D053495:Osteopontin / Q000097:blood*; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000097:blood* / Q000401:mortality / Q000628:therapy; D011013:Pneumonectomy; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D005971:Glutamates; C000715527:MSLN protein, human; D000068437:Pemetrexed; D053495:Osteopontin; D006147:Guanine; D000090204:Mesothelin; D002945:Cisplatin