PMID- 31323001 OWN - NLM STAT- MEDLINE DCOM- 20200917 LR - 20210213 IS - 1437-4331 (Electronic) IS - 1434-6621 (Linking) VI - 57 IP - 12 DP - 2019 Nov 26 TI - EGFR and EGFR ligands in serum in healthy women; reference intervals and age dependency. PG - 1948-1955 LID - 10.1515/cclm-2019-0376 [doi] AB - 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 alpha (TGF-alpha) 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-alpha 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-alpha, 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-alpha. FAU - Kjaer, Ina Mathilde AU - Kjaer IM AUID- ORCID: 0000-0002-6351-379X AD - Department of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Olsen, Dorte Aalund AU - Olsen DA AD - Department of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark. FAU - Alnor, Anne AU - Alnor A AUID- ORCID: 0000-0002-6131-8886 AD - Department of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark. FAU - Brandslund, Ivan AU - Brandslund I AUID- ORCID: 0000-0002-4203-5442 AD - Department of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Bechmann, Troels AU - Bechmann T AUID- ORCID: 0000-0001-6838-6745 AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. AD - Department of Oncology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark. FAU - Madsen, Jonna Skov AU - Madsen JS AUID- ORCID: 0000-0001-6668-4714 AD - Department of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article PL - Germany TA - Clin Chem Lab Med JT - Clinical chemistry and laboratory medicine JID - 9806306 RN - 0 (Amphiregulin) RN - 0 (Betacellulin) RN - 0 (Biomarkers) RN - 0 (EGF Family of Proteins) RN - 0 (Heparin-binding EGF-like Growth Factor) RN - 0 (Ligands) RN - 0 (Transforming Growth Factor alpha) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adult MH - Aged MH - Amphiregulin/analysis/blood MH - Betacellulin/analysis/blood MH - Biomarkers/blood MH - EGF Family of Proteins/*analysis/blood MH - Epidermal Growth Factor/analysis/blood MH - ErbB Receptors/analysis/blood MH - Female MH - Heparin-binding EGF-like Growth Factor/analysis/blood MH - Humans MH - Ligands MH - Middle Aged MH - Reference Standards MH - Reference Values MH - Transforming Growth Factor alpha/analysis/blood OTO - NOTNLM OT - cancer biomarkers OT - epidermal growth factor receptor OT - epidermal growth factor receptor ligands OT - reference interval OT - serum EDAT- 2019/07/20 06:00 MHDA- 2020/09/18 06:00 CRDT- 2019/07/20 06:00 PHST- 2019/04/07 00:00 [received] PHST- 2019/06/17 00:00 [accepted] PHST- 2019/07/20 06:00 [pubmed] PHST- 2020/09/18 06:00 [medline] PHST- 2019/07/20 06:00 [entrez] AID - cclm-2019-0376 [pii] AID - 10.1515/cclm-2019-0376 [doi] PST - ppublish SO - Clin Chem Lab Med. 2019 Nov 26;57(12):1948-1955. doi: 10.1515/cclm-2019-0376.