Editors' ChoiceMesothelioma

To Catch a Fish

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Science Translational Medicine  24 Oct 2012:
Vol. 4, Issue 157, pp. 157ec191
DOI: 10.1126/scitranslmed.3005177

Malignant mesothelioma—the most dreaded complication of asbestos exposure—is an aggressive cancer of the pleura (the external lining of the lung). It has a very poor prognosis and is difficult to detect early, when intervention may be most likely to prolong life. As such, scientists have been searching for years for a biomarker—particularly one that could be measured in plasma—that could be used to screen apparently healthy patients at risk for this disease. With a new study of the extracellular matrix protein fibulin-3, Pass and colleagues have now taken an important step toward identifying such a biomarker.

The authors began their hunt for a useful biomarker by analyzing gene expression in 37 mesothelioma tissue samples taken from patients during surgery and comparing these with corresponding samples from the (unaffected) lining of the abdomen in the same patients. This analysis led to identification of fibulin-3 as a gene with elevated expression in the mesothelioma samples, suggesting that it might be a useful biomarker of disease. The authors then went on to measure fibulin-3 protein levels in plasma and pleural effusions (abnormal fluid accumulations surrounding the lung) from patients with mesothelioma, patients with benign effusions, patients with malignant effusions from other types of cancer, and healthy controls with and without asbestos exposure. Plasma fibulin-3 concentrations were significantly higher in patients with malignant mesothelioma than in asbestos-exposed patients without mesothelioma; likewise, fibulin-3 concentrations in effusion fluid were significantly greater in malignant mesothelioma effusions than benign effusions. Fibulin-3’s association with disease was somewhat less robust in a validation cohort, but it still showed an area under the curve (plasma) of 0.87.

Fibulin-3 is not a perfect stand-alone biomarker for mesothelioma; that is, it does not discriminate between benign and malignant disease with 100% sensitivity and specificity. In addition, it remains to be seen whether screening for elevated plasma fibulin-3 concentrations in high-risk populations would increase early detection of mesothelioma or improve outcomes. Nevertheless, this study moves us toward early detection of this terrible disease. In addition, these results strengthen the argument that discovery genomic and proteomic analyses are more than just expensive fishing expeditions. Indeed, as demonstrated by Pass et al., they can facilitate the identification of much-needed new diagnostic biomarkers.

H. I. Pass, S. M. Levin, M. R. Harbut, J. Melamed, L. Chiriboga, J. Donington, M. Huflejt, M. Carbone, D. Chia, L. Goodglick, G. E. Goodman, M. D. Thornquist, G. Liu, M. de Perrot, M.-S. Tsao, C. Goparaju, Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. N. Engl. J. Med. 367, 1417–1427 (2012). [Abstract]

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