Fibulin-3 as a Biomarker for Pleural Mesothelioma

To the Editor

Pass et al. (Oct. 11 issue)¹ report on fibulin-3 as a new soluble biomarker for malignant mesothelioma. The diagnostic accuracy of plasma levels of fibulin-3 in the Detroit and New York cohorts (area under the receiver-operating-characteristic curve [AUC], 0.99) exceeded that of any previously reported marker. In the external validation cohort, however, the diagnostic accuracy surprisingly decreased (AUC, 0.87). This marked decrease was probably due to differences in the study population, although the study showed no association between plasma fibulin-3 levels and common patient characteristics. To fully comprehend the potential and limitations of this new biomarker, researchers should identify the factors that affect plasma fibulin-3 levels. Of note, the AUC of 0.87 in the validation cohort is similar to what has previously been reported for serum mesothelin, the standard biomarker for mesothelioma (AUC, 0.72 to 0.93).² Data are lacking from matched analyses to elucidate how fibulin-3 compares or combines with mesothelin. Overall, future validation efforts should continue focusing on the performance of fibulin-3 in early-stage disease and maintain the high standards of the study by Pass et al.