Clinical utility of diagnostic biomarkers in malignant pleural mesothelioma: a systematic review and meta-analysis

Abstract

Malignant pleural mesothelioma (MPM) is characterised by late-stage diagnosis and poor prognosis. Currently, no screening tool is advocated and diagnosis is based on invasive techniques, which are not well tolerated. Non-invasive diagnostic biomarkers have shown potential and could have a huge clinical benefit. However, despite extensive research, there is no consensus yet on their clinical use, with many articles reporting contradicting results, limiting their clinical implementation. The aim of this systematic review is therefore to explore the different semi- and non-invasive diagnostic markers in several human matrices and identify those that might clinically be relevant. A total of 100 articles were selected through Web of Science and PubMed, with 56 articles included in the quantitative analysis. Although many studies have reported on the diagnostic accuracy of MPM biomarkers such as serum mesothelin and high-mobility group box protein 1 and plasma fibulin-3, none have resulted in a validated test for early detection. Future research should focus on external validation, combinations into biomarker panels, the inclusion of early stage MPM patients and a combination of different biomarker matrices, as well as new markers.

The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling

“…In agreement, Fibulin-3 has been shown to increase in normal mesothelial cells only after exposure to fluoro-edenite ( 53 ), a mineral fiber that facilitates the malignant transformation of these cells ( 54 ). Several studies have compared the expression of fibulin-3 against other candidate biomarkers in MPM, concluding that the detection of this protein alone may be insufficient to predict patient survival but can provide positive identification of MPM patients and could be useful for patient selection and stratification before treatment ( 55 – 57 ). It should be noted that fibulin-3 remains controversial as a biomarker ( 14 ), even though the original observations of circulating fibulin-3 in MPM patients in the US ( 13 ) have been validated in blinded fashion in population cohorts from Turkey ( 28 ), China ( 29 ) and Egypt ( 30 ).…”

Asbestos-Related Diseases and Policies: an Update

“…Diagnosis of MPM on cytomorphological grounds is challenging, especially when reactive atypical mesothelial cells are present [53,54]. Notwithstanding the plethora of markers, none has been sufficiently specific [48,55]. A tumor diagnosed as MPM using algorithms and panels is not necessarily different from other cancers.…”

Asbestos and anti-asbestos activism: medical and economical aspects

“…Diagnosis of MPM on cytomorphological grounds is challenging, especially when reactive atypical mesothelial cells are present (Blyth and Murphy 2018;Eccher et al 2021). Notwithstanding the plethora of markers, none has been sufficiently specific (Ferrari et al 2020;Schillebeeckx et al 2021). A tumor diagnosed as MPM using algorithms and panels is not necessarily different from other cancers.…”