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. 2021 May 18;13(10):2445.
doi: 10.3390/cancers13102445.

Liquid Biopsies from Pleural Effusions and Plasma from Patients with Malignant Pleural Mesothelioma: A Feasibility Study

Gabriele Moretti  1 , Paolo Aretini  2 , Francesca Lessi  2 , Chiara Maria Mazzanti  2 , Guntulu Ak  3   4 , Muzaffer Metintaş  3   4 , Cecilia Lando  5 , Rosa Angela Filiberti  5 , Marco Lucchi  6 , Alessandra Bonotti  7 , Rudy Foddis  8 , Alfonso Cristaudo  8 , Andrea Bottari  1 , Alessandro Apollo  1 , Marzia Del Re  9 , Romano Danesi  9 , Luciano Mutti  10 , Federica Gemignani  1 , Stefano Landi  1
Affiliations

Liquid Biopsies from Pleural Effusions and Plasma from Patients with Malignant Pleural Mesothelioma: A Feasibility Study

Gabriele Moretti et al. Cancers (Basel). .

Abstract

Background: Malignant pleural mesothelioma (MPM) is a fatal tumor with a poor prognosis. The recent developments of liquid biopsies could provide novel diagnostic and prognostic tools in oncology. However, there is limited information about the feasibility of this technique for MPMs. Here, we investigate whether cancer-specific DNA sequences can be detected in pleural fluids and plasma of MPM patients as free circulating tumor DNA (ctDNA).

Methods: We performed whole-exome sequencing on 14 tumor biopsies from 14 patients, and we analyzed 20 patient-specific somatic mutations with digital droplet PCR (ddPCR) in pleural fluids and plasma, using them as cancer-specific tumor biomarkers.

Results: Most of the selected mutations could be detected in pleural fluids (94%) and, noteworthy, in plasma (83%) with the use of ddPCR. Pleural fluids showed similar levels of somatically mutated ctDNA (median = 12.75%, average = 16.3%, standard deviation = 12.3) as those detected in solid biopsies (median = 21.95%; average = 22.21%; standard deviation = 9.57), and their paired difference was weakly statistically significant (p = 0.048). On the other hand, the paired difference between solid biopsies and ctDNA from plasma (median = 0.29%, average = 0.89%, standard deviation = 1.40) was highly statistically significant (p = 2.5 × 10-7), corresponding to the important drop of circulating somatically mutated DNA in the bloodstream. However, despite the tiny amount of ctDNA in plasma, varying from 5.57% down to 0.14%, the mutations were detectable at rates similar to those possible for other tumors.

Conclusions: We found robust evidence that mutated DNA is spilled from MPMs, mostly into pleural fluids, proving the concept that liquid biopsies are feasible for MPM patients.

Keywords: cancer biomarkers; cancer-specific mutations; circulating tumor DNA; genomics; liquid biopsies; malignant pleural mesothelioma; plasma.

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Conflict of interest statement

The authors declare there is no conflict of interest. The founding entity had no role in the writing of the manuscript and the performing of the study; in the collection, analyses, or interpretation of data; and in the decision to publish the results.

Figures

Figure 1
Figure 1
Mean levels of mutated DNA found in the samples from three sources: solid tumor, pleural fluid, and plasma.
See this image and copyright information in PMC

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