Fibulin-3 as a Diagnostic Biomarker in Patients with Malignant Mesothelioma

Abstract

Background: New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. Materials and Methods: This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. Results: Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). Conclusions: We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.

Diagnostic and prognostic utilities of humoral fibulin-3 in malignant pleural mesothelioma: Evidence from a meta-analysis

“…Eight eligible studies then received full text evaluation, and in one of them, the ROC curve analysis compared the status of fibulin-3 in monitoring chemotherapy response of MPM, data from which were eventually eliminated [19]. Last, 6 studies for diagnosis [9, 10, 12, 14, 15, 17], and 3 for prognosis [10, 15, 16], were enrolled for the meta-analysis.…”

“…Recent findings have documented the significantly altered expression status of humoral fibulin-3 in mesothelioma, thereby highlighting its promising application as a novel biomarker for MPM diagnosis and prognosis [9–18]. Nevertheless, single study often presented with inaccurate and insufficient information due to restrictions from limited sample size and research programs.…”

Overexpressed genes in malignant pleural mesothelioma: implications in clinical management

“…The first evidence of the diagnostic value of fibulin-3 appeared in 2012 (83), but in 2014 these data were not confirmed and soluble mesothelin related peptide was declared a more potent diagnostic marker in serum than fibulin-3 (25). In 2015 its diagnostic value has been claimed again with the observation that MPM patients had significantly higher serum levels of fibulin-3 than controls (84). Two subsequent studies in 2015 and 2017, did not confirmed this result and declared FBLN3 detection in pleural effusion not useful as a biomarker for the diagnosis of MPM (29).…”

Serum mesothelin and other biomarkers: what have we learned in the last decade?

“…Other authors considered that the real use for serum fibulin-3 was for diagnosis in MPM but not for prognosis (30).…”

“…Several studies have investigated the diagnostic value of fibulin-3 for MPM and based on these fibulin-3 results a useful diagnostic marker for MPM (30)(31)(32)(33)(34).…”