EGFR and EGFR ligands in serum in healthy women; reference intervals and age dependency
-
Ina Mathilde Kjær
, Dorte Aalund Olsen
, Anne Alnor, Ivan Brandslund
, Troels Bechmann
und Jonna Skov Madsen
Abstract
Background
The epidermal growth factor receptor (EGFR) system is involved in cancer pathogenesis and serves as an important target for multiple cancer treatments. EGFR and its ligands epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF), betacellulin (BTC), amphiregulin (AREG) and transforming growth factor α (TGF-α) have potential applications as prognostic or predictive serological biomarkers in cancer. The aim was to establish EGFR and EGFR ligand reference intervals in healthy women.
Methods
EGFR and EGFR ligands were measured in serum from 419 healthy women aged 26–78 years. The need for age partitioned reference intervals was evaluated using Lahti’s method. EGFR and EGF were analyzed using ELISA assays, whereas HB-EGF, BTC, AREG and TGF-α were analyzed using the highly sensitive automated single molecule array (Simoa) enabling detection below the lower reference limit for all six biomarkers.
Results
Reference intervals for EGFR and the EGFR ligands were determined as the 2.5th and 97.5th percentiles. All six biomarkers were detectable in all serum samples. For EGFR, EGF, HB-EGF and TGF-α, reference intervals were established for women <55 years and for women >55 years, whilst common reference intervals were established for AREG and BTC including women aged 26–78 years.
Conclusions
Age specific reference intervals were determined for EGFR, EGF, HB-EGF, BTC, AREG and TGF-α.
Acknowledgments
Oluf Borbye Pedersen, Torben Hansen, and Cramer Christensen are acknowledged for providing the blood samples from Vejle Diabetes Biobank to the study. Assistant Jannie Møller and laboratory technicians Camilla Davidsen and Sara Egsgaard are acknowledged for their excellent contributions to this work. OPEN, Patient data Explorative Network, Odense University Hospital, Odense, Denmark are acknowledged for the collaboration on data management.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: The study was supported by grants from the Research Committee, Lillebaelt Hospital, Vejle, Denmark, the Region of Southern Denmark, and from the University of Southern Denmark.
Employment or leadership: Ivan Brandslund is a member of the editorial board of Clinical Chemistry and Laboratory Medicine.
Honorarium: None declared.
Competing interests: No funding organization played a role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2019 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- The re-emergence of dried blood spot sampling – are we ready?
- Review
- The role of platelets in bleeding in patients with thrombocytopenia and hematological disease
- Opinion Paper
- Exertional hematuria: definition, epidemiology, diagnostic and clinical considerations
- Guidelines and Recommendations from Scientific Societies
- A protocol for testing the stability of biochemical analytes. Technical document
- Genetics and Molecular Diagnostics
- Hereditary hyperferritinaemia-cataract syndrome (HHCS) – an underestimated condition: ferritin light chain variant spectrum in German families
- General Clinical Chemistry and Laboratory Medicine
- Performance of a web-based application measuring spot quality in dried blood spot sampling
- Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients
- Plasma and dried blood spot lysosphingolipids for the diagnosis of different sphingolipidoses: a comparative study
- Liquid biopsy of cerebrospinal fluid identifies neuronal pentraxin receptor (NPTXR) as a biomarker of progression of Alzheimer’s disease
- Integrity of serum samples is changed by modified centrifugation conditions
- Heparin and citrate additive carryover during blood collection
- Copeptin – a biomarker of short-term mortality risk (7 days) in patients with end-stage liver disease
- Comparison of a new rapid method for the determination of adalimumab serum levels with two established ELISA kits
- Measurement of α-dicarbonyl compounds in human saliva by pre-column derivatization HPLC
- Establishment of the intelligent verification criteria for a routine urinalysis analyzer in a multi-center study
- Reference Values and Biological Variations
- A new indirect estimation of reference intervals: truncated minimum chi-square (TMC) approach
- EGFR and EGFR ligands in serum in healthy women; reference intervals and age dependency
- Early pregnancy reference intervals; 29 serum analytes from 4 to 12 weeks’ gestation in naturally conceived and uncomplicated pregnancies resulting in live births
- Paediatric reference intervals for 17 Roche cobas 8000 e602 immunoassays in the CALIPER cohort of healthy children and adolescents
- Hematology and Coagulation
- Study of the analytical performance at different concentrations of hematological parameters using Spanish EQAS data
- Multicenter performance evaluation of the Abbott Alinity hq hematology analyzer
- Cardiovascular Diseases
- Fast 0/1-h algorithm for detection of NSTEMI: are current high-sensitivity cardiac troponin assays fit for purpose? An EQA-based evaluation
- Infectious Diseases
- Diagnostic performance of cerebrospinal fluid free light chains in Lyme neuroborreliosis – a pilot study
- Letters to the Editor
- Quality management at the national biobanking level – establishing a culture of mutual trust and support: the BBMRI.at example
- Molecular diagnosis of MODY3 permitted to reveal a de novo 12q24.31 deletion and to explain a complex phenotype in a young diabetic patient
- Increased C-reactive protein values in the absence of inflammation: monoclonal immunoglobulin interference in immunonephelometry
- An approach based on simulated hemolysis for establishing the hemolysis index threshold for high-sensitivity cardiac troponin T assay
- Utility of the icteric index for the management of bilirubin test requesting
- Quality control of monocyte volume and distribution width parameters of the Beckman Coulter DxH series
- Mozhaisk haemoglobin variant effects on leukocyte differential channel using the Sysmex XN series
- Detection of a novel hemoglobin variant Hb Liaoning by matrix assisted laser desorption/ionization-time of flight mass spectrometry
- Appropriateness of repetitive therapeutic drug monitoring and laboratory turnaround time
- Congress Abstracts
- 51th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
Artikel in diesem Heft
- Frontmatter
- Editorial
- The re-emergence of dried blood spot sampling – are we ready?
- Review
- The role of platelets in bleeding in patients with thrombocytopenia and hematological disease
- Opinion Paper
- Exertional hematuria: definition, epidemiology, diagnostic and clinical considerations
- Guidelines and Recommendations from Scientific Societies
- A protocol for testing the stability of biochemical analytes. Technical document
- Genetics and Molecular Diagnostics
- Hereditary hyperferritinaemia-cataract syndrome (HHCS) – an underestimated condition: ferritin light chain variant spectrum in German families
- General Clinical Chemistry and Laboratory Medicine
- Performance of a web-based application measuring spot quality in dried blood spot sampling
- Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients
- Plasma and dried blood spot lysosphingolipids for the diagnosis of different sphingolipidoses: a comparative study
- Liquid biopsy of cerebrospinal fluid identifies neuronal pentraxin receptor (NPTXR) as a biomarker of progression of Alzheimer’s disease
- Integrity of serum samples is changed by modified centrifugation conditions
- Heparin and citrate additive carryover during blood collection
- Copeptin – a biomarker of short-term mortality risk (7 days) in patients with end-stage liver disease
- Comparison of a new rapid method for the determination of adalimumab serum levels with two established ELISA kits
- Measurement of α-dicarbonyl compounds in human saliva by pre-column derivatization HPLC
- Establishment of the intelligent verification criteria for a routine urinalysis analyzer in a multi-center study
- Reference Values and Biological Variations
- A new indirect estimation of reference intervals: truncated minimum chi-square (TMC) approach
- EGFR and EGFR ligands in serum in healthy women; reference intervals and age dependency
- Early pregnancy reference intervals; 29 serum analytes from 4 to 12 weeks’ gestation in naturally conceived and uncomplicated pregnancies resulting in live births
- Paediatric reference intervals for 17 Roche cobas 8000 e602 immunoassays in the CALIPER cohort of healthy children and adolescents
- Hematology and Coagulation
- Study of the analytical performance at different concentrations of hematological parameters using Spanish EQAS data
- Multicenter performance evaluation of the Abbott Alinity hq hematology analyzer
- Cardiovascular Diseases
- Fast 0/1-h algorithm for detection of NSTEMI: are current high-sensitivity cardiac troponin assays fit for purpose? An EQA-based evaluation
- Infectious Diseases
- Diagnostic performance of cerebrospinal fluid free light chains in Lyme neuroborreliosis – a pilot study
- Letters to the Editor
- Quality management at the national biobanking level – establishing a culture of mutual trust and support: the BBMRI.at example
- Molecular diagnosis of MODY3 permitted to reveal a de novo 12q24.31 deletion and to explain a complex phenotype in a young diabetic patient
- Increased C-reactive protein values in the absence of inflammation: monoclonal immunoglobulin interference in immunonephelometry
- An approach based on simulated hemolysis for establishing the hemolysis index threshold for high-sensitivity cardiac troponin T assay
- Utility of the icteric index for the management of bilirubin test requesting
- Quality control of monocyte volume and distribution width parameters of the Beckman Coulter DxH series
- Mozhaisk haemoglobin variant effects on leukocyte differential channel using the Sysmex XN series
- Detection of a novel hemoglobin variant Hb Liaoning by matrix assisted laser desorption/ionization-time of flight mass spectrometry
- Appropriateness of repetitive therapeutic drug monitoring and laboratory turnaround time
- Congress Abstracts
- 51th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)