title: Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer.
abstract: 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.
authors: Thoracic Surgery Unit, Department of Cardiology, Thoracic and Vascular Surgery, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. filippo.lococo@asmn.re.it.
authors: Filippo
authors: F
authors: Lococo
authors: Thoracic Surgery Unit, Department of Cardiology, Thoracic and Vascular Surgery, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. massimiliano.paci@asmn.re.it.
authors: Massimiliano
authors: M
authors: Paci
authors: Thoracic Surgery Unit, Department of Cardiology, Thoracic and Vascular Surgery, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. cristian.rapicetta@asmn.re.it.
authors: Cristian
authors: C
authors: Rapicetta
authors: Laboratory of Translational Research, Research and Statistic Infrastructure, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. teresa.rossi@asmn.re.it.
authors: Teresa
authors: T
authors: Rossi
authors: Laboratory of Translational Research, Research and Statistic Infrastructure, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. valentina.sancisi@asmn.re.it.
authors: Valentina
authors: V
authors: Sancisi
authors: Clinical Trials and Statistics Unit, Department of Infrastructure Research and Statistics, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. luca.braglia@asmn.re.it.
authors: Luca
authors: L
authors: Braglia
authors: Clinical Trials and Statistics Unit, Department of Infrastructure Research and Statistics, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. silvio.cavuto@asmn.re.it.
authors: Silvio
authors: S
authors: Cavuto
authors: Pathology Unit, Department of Oncology and Advanced Technologies, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. alessandra.bisagni@asmn.re.it.
authors: Alessandra
authors: A
authors: Bisagni
authors: Proteomics Laboratory, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan 20133, Italy. italia.bongarzone@istitutotumori.mi.it.
authors: Italia
authors: I
authors: Bongarzone
authors: Department of Biotechnology and Life Sciences, University of Insubria, Varese 21100, Italy. douglas.noonan@uninsubria.it.|Scientific and Technology Park, IRCCS MultiMedica, Milan 20138, Italy. douglas.noonan@uninsubria.it.
authors: Douglas M
authors: DM
authors: Noonan
authors: Laboratory of Translational Research, Research and Statistic Infrastructure, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. adriana.albini@asmn.re.it.
authors: Adriana
authors: A
authors: Albini
authors: Laboratory of Translational Research, Research and Statistic Infrastructure, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia 42123, Italy. sally.maramotti@asmn.re.it.
authors: Sally
authors: S
authors: Maramotti
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D055088:Early Detection of Cancer; D066246:ErbB Receptors / Q000097:blood*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR isoform (sEGFR); Epidermal growth factor receptor (EGFR); biomarker; diagnosis; non-small cell lung cancer (NSCLC)