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. 2020 May 13:8:15.
doi: 10.1186/s40364-020-00194-4. eCollection 2020.

Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies

Daniel G Weber  1 , Swaantje Casjens  1 , Alexander Brik  1 , Irina Raiko  1 , Martin Lehnert  1 , Dirk Taeger  1 , Jan Gleichenhagen  1 , Jens Kollmeier  2 , Torsten T Bauer  2 , Thomas Brüning  1 , Georg Johnen  1 ; MoMar study group
Collaborators, Affiliations

Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies

Daniel G Weber et al. Biomark Res. .

Abstract

Background: For the detection of malignant mesothelioma additional markers are needed besides the established panel consisting of calretinin and mesothelin. The aim of this study was the identification and verification of long non-coding RNAs (lncRNAs) as complementing circulating markers.

Methods: Candidate lncRNAs were identified in silico using previously published RNA expression profiles and verified using quantitative PCR (qPCR) in mesothelioma cell lines as well as human plasma samples from mesothelioma patients and asbestos-exposed controls.

Results: GAS5 (growth arrest-specific transcript 5) as a single marker is marked by a low sensitivity of 14%, but the combination of GAS5 with calretinin and mesothelin increased the panel's sensitivity from 64 to 73% at a predefined specificity of 97%. Circulating GAS5 is not affected by pleurectomy before blood collection, age, or smoking status.

Conclusions: GAS5 is verified as an appropriate circulating marker for the supplement of calretinin and mesothelin to detect malignant mesothelioma. Although the sensitivity of GAS5 is too low for the use as a single marker, the addition of GAS5 as a third marker improves the performance of the established marker panel. The benefit of GAS5 for the detection of malignant mesothelioma at early stages needs to be validated in a prospective study.

Keywords: Biomarker; Blood; Cancer; Circulating; Early detection; Liquid biopsy; Marker; Mesothelioma; Plasma; Screening; lncRNA; qPCR.

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Conflict of interest statement

Competing interestsThe IPA has supplied DLD Diagnostika GmbH with the antibodies to produce the Calretinin ELISA kits. In turn, the IPA has received Calretinin ELISA kits at a reduced price and may benefit from future sales of the kits. Otherwise, the individual authors declare no competing interests.

Figures

Fig. 1
Fig. 1
a Distribution of normalized GAS5 in plasma of mesothelioma patients and asbestos-exposed controls. b Receiver operating characteristic (ROC) curve of circulating GAS5
Fig. 2
Fig. 2
a Distribution of calretinin in plasma of mesothelioma patients and asbestos-exposed controls. b Distribution of mesothelin in plasma of mesothelioma patients and asbestos-exposed controls. c Receiver operating characteristics (ROC) curves of calretinin, mesothelin, and sequential combination of calretinin and mesothelin
Fig. 3
Fig. 3
Receiver operating characteristics (ROC) curves of linear and sequential combination using GAS5, calretinin, and mesothelin
See this image and copyright information in PMC

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