Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical manag...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2015-08-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | http://www.mdpi.com/1422-0067/16/8/19612 |
id |
doaj-5cf9746e6c8146dc9f62a4a3a2e38e5d |
---|---|
record_format |
Article |
spelling |
doaj-5cf9746e6c8146dc9f62a4a3a2e38e5d2020-11-25T02:34:42ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-08-01168196121963010.3390/ijms160819612ijms160819612Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung CancerFilippo Lococo0Massimiliano Paci1Cristian Rapicetta2Teresa Rossi3Valentina Sancisi4Luca Braglia5Silvio Cavuto6Alessandra Bisagni7Italia Bongarzone8Douglas M. Noonan9Adriana Albini10Sally Maramotti11Thoracic Surgery Unit, Department of Cardiology, Thoracic and Vascular Surgery, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyThoracic Surgery Unit, Department of Cardiology, Thoracic and Vascular Surgery, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyThoracic Surgery Unit, Department of Cardiology, Thoracic and Vascular Surgery, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyLaboratory of Translational Research, Research and Statistic Infrastructure, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyLaboratory of Translational Research, Research and Statistic Infrastructure, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyClinical Trials and Statistics Unit, Department of Infrastructure Research and Statistics, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyClinical Trials and Statistics Unit, Department of Infrastructure Research and Statistics, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyPathology Unit, Department of Oncology and Advanced Technologies, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyProteomics Laboratory, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan 20133, ItalyDepartment of Biotechnology and Life Sciences, University of Insubria, Varese 21100, ItalyLaboratory of Translational Research, Research and Statistic Infrastructure, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyLaboratory of Translational Research, Research and Statistic Infrastructure, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, ItalyAssessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.http://www.mdpi.com/1422-0067/16/8/19612Epidermal growth factor receptor (EGFR)EGFR isoform (sEGFR)non-small cell lung cancer (NSCLC)biomarkerdiagnosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Filippo Lococo Massimiliano Paci Cristian Rapicetta Teresa Rossi Valentina Sancisi Luca Braglia Silvio Cavuto Alessandra Bisagni Italia Bongarzone Douglas M. Noonan Adriana Albini Sally Maramotti |
spellingShingle |
Filippo Lococo Massimiliano Paci Cristian Rapicetta Teresa Rossi Valentina Sancisi Luca Braglia Silvio Cavuto Alessandra Bisagni Italia Bongarzone Douglas M. Noonan Adriana Albini Sally Maramotti Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer International Journal of Molecular Sciences Epidermal growth factor receptor (EGFR) EGFR isoform (sEGFR) non-small cell lung cancer (NSCLC) biomarker diagnosis |
author_facet |
Filippo Lococo Massimiliano Paci Cristian Rapicetta Teresa Rossi Valentina Sancisi Luca Braglia Silvio Cavuto Alessandra Bisagni Italia Bongarzone Douglas M. Noonan Adriana Albini Sally Maramotti |
author_sort |
Filippo Lococo |
title |
Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer |
title_short |
Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer |
title_full |
Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer |
title_fullStr |
Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer |
title_full_unstemmed |
Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer |
title_sort |
preliminary evidence on the diagnostic and molecular role of circulating soluble egfr in non-small cell lung cancer |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2015-08-01 |
description |
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies. |
topic |
Epidermal growth factor receptor (EGFR) EGFR isoform (sEGFR) non-small cell lung cancer (NSCLC) biomarker diagnosis |
url |
http://www.mdpi.com/1422-0067/16/8/19612 |
work_keys_str_mv |
AT filippolococo preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT massimilianopaci preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT cristianrapicetta preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT teresarossi preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT valentinasancisi preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT lucabraglia preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT silviocavuto preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT alessandrabisagni preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT italiabongarzone preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT douglasmnoonan preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT adrianaalbini preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer AT sallymaramotti preliminaryevidenceonthediagnosticandmolecularroleofcirculatingsolubleegfrinnonsmallcelllungcancer |
_version_ |
1724807169590689792 |