Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma.

Abstract

INTRODUCTION:

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: Kevin Hollevoet, Kristiaan Nackaerts, Robert Gosselin, Walter De Wever, Lionel Bosquée, Paul De Vuyst, Paul Germonpré, Eliane Kellen, Catherine Legrand, Yoshiro Kishi, Joris R Delanghe, Jan P van Meerbeeck
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 6 Issue 11 Pg. 1930-7 (Nov 2011) ISSN: 1556-1380 [Electronic] United States
• PMID: 21841505 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• GPI-Linked Proteins
• Glutamates
• MSLN protein, human
• Pemetrexed
• Osteopontin
• Guanine
• Mesothelin
• Cisplatin

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (blood)
• Cisplatin (administration & dosage)
• Combined Modality Therapy
• Enzyme-Linked Immunosorbent Assay
• Female
• Follow-Up Studies
• GPI-Linked Proteins (blood)
• Glutamates (administration & dosage)
• Guanine (administration & dosage, analogs & derivatives)
• Humans
• Male
• Mesothelin
• Mesothelioma (blood, mortality, therapy)
• Middle Aged
• Neoplasm Staging
• Osteopontin (blood)
• Pemetrexed
• Pleural Neoplasms (blood, mortality, therapy)
• Pneumonectomy
• Prognosis
• Prospective Studies
• Survival Rate
• Tomography, X-Ray Computed