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

Our plain-English summary of Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis, by B. Mosleh, K. Schelch, T. Mohr, et al (Thoracic Cancer, 2023).

The study

• Authors: B. Mosleh, K. Schelch, T. Mohr, T. Klikovits, C. Wagner, L. Ratzinger, Y. Dong, K. Sinn, A. Ries, W. Berger, B. Grasl-Kraupp, K. Hoetzenecker, V. Laszlo, B. Dome, B. Hegedus, M. Jakopovic, M.A. Hoda, M. Grusch
• Journal: Thoracic Cancer
• Published: 2023;14(22):2177-2186
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

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

In plain English

This laboratory and patient study looked at a growth factor called FGF18 in pleural mesothelioma. The authors measured FGF18 gene activity in cell lines and in a public dataset of 85 patients. They altered two mesothelioma cell lines to make extra FGF18. They also measured FGF18 in blood plasma from three groups: 40 pleural mesothelioma patients from Vienna and Zagreb, 40 healthy people, and six patients with benign pleural fibrosis (two of them asbestos-induced). Mesothelioma cell lines showed high FGF18 gene activity. In the blood, however, median FGF18 was lower in mesothelioma patients (112.3 pg/mL) than in healthy controls (192.4 pg/mL). It was also lower in the fibrosis patients (115.5 pg/mL). Mesothelioma and fibrosis patients did not differ significantly. Blood FGF18 did not differ between the 25 patients with and the 15 without asbestos exposure recorded in their history. It was not significantly linked to stage or survival. The authors concluded that their data disprove circulating FGF18 as a prognostic biomarker in pleural mesothelioma. They noted that small numbers of fibrosis and nonepithelioid patients are a limitation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study (cell lines, analysis of public TCGA gene data) combined with a blood biomarker study comparing patients with healthy and benign-disease controls
• Who was studied: Plasma from 40 patients with histologically confirmed pleural mesothelioma (29 from the Medical University of Vienna, 11 from University Hospital Centre Zagreb, Croatia). Controls were 40 healthy individuals and six patients with benign pleural diseases: 2 with asbestos-induced diffuse pleural fibrosis, 3 with inflammation-induced pleural fibrosis of unknown origin, and 1 with hyaluronan-induced pleural fibrosis. The study also used TCGA gene data from 85 PM patients and eight PM cell lines.
• Exposure: The main factor studied was the growth factor FGF18 (gene expression and blood levels), not asbestos. Asbestos exposure was recorded from patient history: 25 mesothelioma patients with exposure and 15 without. No fiber types or doses were given.
• Main results:
  • In the TCGA dataset of 85 PM patients, high FGF18 gene expression showed a trend toward longer overall survival that was not statistically significant. Median survival was 17.867 months in the low group vs 20.267 months in the high group (HR 1.397, 95% CI 0.867–2.250, p = 0.168).
  • In the SPC212 mesothelioma cell line, forced overexpression of FGF18 significantly reduced clonogenic growth compared with the vector control. In the M38K cell line there was no difference.
  • SPC212 cells overexpressing FGF18 showed a significant increase in cell migration. M38K cells showed no change.
  • Median plasma FGF18 was significantly lower in the 40 PM patients (112.3 pg/mL, IQR 79.7–142.5) than in the 40 healthy controls (192.4 pg/mL, IQR 151.8–230.4; p less than 0.001).
  • Median plasma FGF18 was also significantly lower in the 6 benign fibrosis patients (115.5 pg/mL, IQR 99.4–142.4) than in healthy controls (p = 0.004).
  • No significant difference in plasma FGF18 was found between PM patients and fibrosis patients (p = 0.974).
  • In ROC analysis separating healthy individuals from PM patients, plasma FGF18 had an area under the curve of 0.837.
  • Plasma FGF18 did not differ between PM patients with early-stage and advanced disease. It also did not differ between those with (n = 25) and without (n = 15) anamnestically established asbestos exposure.
  • Among PM patients, those with low plasma FGF18 had longer, but not significantly longer, overall survival than those with high levels. Median survival was 24.167 vs 18.900 months (HR 0.821, 95% CI 0.378–1.783, p = 0.618).
  • In multivariate analysis, FGF18 was not an independent prognostic factor for overall survival (low vs high; HR 0.820, 95% CI 0.330–2.039, p = 0.632). No independent predictors were detected.
• The authors' conclusion: The authors concluded that their data disprove circulating FGF18 as a prognostic biomarker in pleural mesothelioma. They said the decrease of circulating FGF18 in pleural disease and its role in PM biology should be further evaluated.
• Limitations the authors state:
  • Some results, especially those for patients with fibrosis and with nonepithelioid PM, rest on small sample numbers.
  • Because PM patients did not differ significantly from pleural fibrosis patients, the authors said FGF18's usefulness for diagnosis may be limited.
  • BAP1 status was not available for the patient cohort.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Mesothelium, Biomarker, Fibrosis, Overall Survival.

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