Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis.


Journal

Thoracic cancer
ISSN: 1759-7714
Titre abrégé: Thorac Cancer
Pays: Singapore
ID NLM: 101531441

Informations de publication

Date de publication:
08 2023
Historique:
revised: 02 06 2023
received: 07 04 2023
accepted: 05 06 2023
medline: 4 8 2023
pubmed: 21 6 2023
entrez: 21 6 2023
Statut: ppublish

Résumé

Pleural mesothelioma (PM) is a relatively rare malignancy with limited treatment options and dismal prognosis. We have previously found elevated FGF18 expression in PM tissue specimens compared with normal mesothelium. The objective of the current study was to further explore the role of FGF18 in PM and evaluate its suitability as a circulating biomarker. FGF18 mRNA expression was analyzed by real-time PCR in cell lines and in silico in datasets from the Cancer Genome Atlas (TCGA). Cell lines overexpressing FGF18 were generated by retroviral transduction and cell behavior was investigated by clonogenic growth and transwell assays. Plasma was collected from 40 PM patients, six patients with pleural fibrosis, and 40 healthy controls. Circulating FGF18 was measured by ELISA and correlated to clinicopathological parameters. FGF18 showed high mRNA expression in PM and PM-derived cell lines. PM patients with high FGF18 mRNA expression showed a trend toward longer overall survival (OS) in the TCGA dataset. In PM cells with low endogenous FGF18 expression, forced overexpression of FGF18 resulted in reduced growth but increased migration. Surprisingly, despite the high FGF18 mRNA levels observed in PM, circulating FGF18 protein was significantly lower in PM patients and patients with pleural fibrosis than in healthy controls. No significant association of circulating FGF18 with OS or other disease parameters of PM patients was observed. FGF18 is not a prognostic biomarker in PM. Its role in PM tumor biology and the clinical significance of decreased plasma FGF18 in PM patients warrant further investigation.

Sections du résumé

BACKGROUND
Pleural mesothelioma (PM) is a relatively rare malignancy with limited treatment options and dismal prognosis. We have previously found elevated FGF18 expression in PM tissue specimens compared with normal mesothelium. The objective of the current study was to further explore the role of FGF18 in PM and evaluate its suitability as a circulating biomarker.
METHODS
FGF18 mRNA expression was analyzed by real-time PCR in cell lines and in silico in datasets from the Cancer Genome Atlas (TCGA). Cell lines overexpressing FGF18 were generated by retroviral transduction and cell behavior was investigated by clonogenic growth and transwell assays. Plasma was collected from 40 PM patients, six patients with pleural fibrosis, and 40 healthy controls. Circulating FGF18 was measured by ELISA and correlated to clinicopathological parameters.
RESULTS
FGF18 showed high mRNA expression in PM and PM-derived cell lines. PM patients with high FGF18 mRNA expression showed a trend toward longer overall survival (OS) in the TCGA dataset. In PM cells with low endogenous FGF18 expression, forced overexpression of FGF18 resulted in reduced growth but increased migration. Surprisingly, despite the high FGF18 mRNA levels observed in PM, circulating FGF18 protein was significantly lower in PM patients and patients with pleural fibrosis than in healthy controls. No significant association of circulating FGF18 with OS or other disease parameters of PM patients was observed.
CONCLUSIONS
FGF18 is not a prognostic biomarker in PM. Its role in PM tumor biology and the clinical significance of decreased plasma FGF18 in PM patients warrant further investigation.

Identifiants

pubmed: 37340889
doi: 10.1111/1759-7714.15004
pmc: PMC10396789
doi:

Substances chimiques

RNA, Messenger 0
fibroblast growth factor 18 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2177-2186

Subventions

Organisme : Austrian Science Fund FWF
ID : I 3977
Pays : Austria

Informations de copyright

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Références

Cell Physiol Biochem. 2018;49(3):1019-1032
pubmed: 30196303
Oncol Rep. 2018 Aug;40(2):704-714
pubmed: 29901199
Carcinogenesis. 2008 Jan;29(1):15-24
pubmed: 17890768
Clin Cancer Res. 2020 Jul 15;26(14):3819-3830
pubmed: 32317288
Front Oncol. 2020 Sep 29;10:1685
pubmed: 33117668
J Clin Oncol. 2012 May 1;30(13):1541-9
pubmed: 22412141
Mol Cell Biol. 1998 Oct;18(10):6063-74
pubmed: 9742123
Lung Cancer. 2020 Jan;139:124-132
pubmed: 31778960
Eur J Cancer. 2016 Aug;63:64-73
pubmed: 27288871
Int J Mol Sci. 2013 May 06;14(5):9686-702
pubmed: 23648477
J Biol Chem. 2006 Jun 9;281(23):15694-700
pubmed: 16597617
Oncogene. 2019 Jan;38(1):33-46
pubmed: 30082912
J Invest Dermatol. 2011 Oct;131(10):2087-95
pubmed: 21753785
Cells. 2019 Sep 16;8(9):
pubmed: 31527546
Physiology (Bethesda). 2010 Apr;25(2):85-101
pubmed: 20430953
Hepatology. 2011 Mar;53(3):854-64
pubmed: 21319186
Int J Oncol. 2001 May;18(5):1093-8
pubmed: 11295061
Br J Cancer. 2015 Sep 15;113(6):963-9
pubmed: 26263483
Br J Cancer. 2012 Dec 4;107(12):1978-86
pubmed: 23169291
Oncogene. 2020 Oct;39(43):6647-6663
pubmed: 32934314
J Pathol. 1999 Sep;189(1):72-8
pubmed: 10451491
Cancer Sci. 2019 Jan;110(1):180-193
pubmed: 30417500
Cancers (Basel). 2021 Nov 13;13(22):
pubmed: 34830836
Genes Dev. 2002 Apr 1;16(7):870-9
pubmed: 11937494
J Clin Invest. 2013 Oct;123(10):4435-48
pubmed: 24018557
Nat Genet. 2016 Apr;48(4):407-16
pubmed: 26928227
BMC Cancer. 2017 May 30;17(1):386
pubmed: 28558669
Eur Respir Rev. 2021 Nov 17;30(162):
pubmed: 34789461
Neoplasia. 2017 Aug;19(8):649-658
pubmed: 28732212
Am J Respir Crit Care Med. 2014 Oct 1;190(7):763-72
pubmed: 25188816
Mol Cancer Res. 2014 Oct;12(10):1460-9
pubmed: 24966347
Carcinogenesis. 2018 Apr 5;39(4):534-545
pubmed: 29635378
Cancer Res. 2003 Oct 1;63(19):6116-20
pubmed: 14559787
WIREs Mech Dis. 2022 Jul;14(4):e1549
pubmed: 35142107
Lung. 2016 Jun;194(3):409-17
pubmed: 27032653
Lung. 2019 Oct;197(5):641-649
pubmed: 31267149
Exp Cell Res. 2013 Dec 10;319(20):3094-103
pubmed: 23973668
Oncogene. 2018 Mar;37(9):1220-1236
pubmed: 29242604
Clin Cancer Res. 2015 Nov 1;21(21):4960-9
pubmed: 25944803
Brain Res Mol Brain Res. 2002 Sep 30;105(1-2):60-6
pubmed: 12399108
Biochem Biophys Res Commun. 2004 Sep 24;322(3):887-92
pubmed: 15336546
J Thorac Oncol. 2016 Dec;11(12):2089-2099
pubmed: 27687963
EMBO J. 2014 Aug 1;33(15):1713-26
pubmed: 24986882
Clin Cancer Res. 2018 Jan 1;24(1):84-94
pubmed: 29061644
Curr Opin Oncol. 2021 Jan;33(1):80-86
pubmed: 33186182
Thorac Cancer. 2023 Aug;14(22):2177-2186
pubmed: 37340889
Cells. 2019 Sep 16;8(9):
pubmed: 31527449
J Biol Chem. 2005 Jul 8;280(27):25369-76
pubmed: 15878867

Auteurs

Berta Mosleh (B)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Karin Schelch (K)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

Thomas Mohr (T)

Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

Thomas Klikovits (T)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Christina Wagner (C)

Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

Lukas Ratzinger (L)

Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

Yawen Dong (Y)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Katharina Sinn (K)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Alexander Ries (A)

Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

Walter Berger (W)

Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

Bettina Grasl-Kraupp (B)

Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

Konrad Hoetzenecker (K)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Viktoria Laszlo (V)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Balazs Dome (B)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
National Koranyi Institute of Pulmonology, Budapest, Hungary.
Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary.

Balazs Hegedus (B)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Marko Jakopovic (M)

Department for Respiratory Diseases Jordanovac, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.

Mir Alireza Hoda (MA)

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Michael Grusch (M)

Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

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