title: Blood-sampling collection prior to surgery may have a significant influence upon biomarker concentrations measured.
abstract: BACKGROUND
  Biomarkers can be subtle tools to aid the diagnosis, prognosis and monitoring of therapy and disease progression. The validation of biomarkers is a cumbersome process involving many steps. Serum samples from lung cancer patients were collected in the framework of a larger study for evaluation of biomarkers for early detection of lung cancer. The analysis of biomarker levels measured revealed a noticeable difference in certain biomarker values that exhibited a dependence of the time point and setting of the sampling. Biomarker concentrations differed significantly if taken before or after the induction of anesthesia and if sampled via venipuncture or arterial catheter.
  
  
  METHODS
  To investigate this observation, blood samples from 13 patients were drawn 1-2 days prior to surgery (T1), on the same day by venipuncture (T2) and after induction of anesthesia via arterial catheter (T3). The biomarkers Squamous Cell Carcinoma antigen (CanAG SCC EIA, Fujirebio Diagnostics, Malvern, USA), Carcinoembrionic Antigen (CEA), and CYFRA 21-1 (Roche Diagnostics GmbH, Mannheim, Germany) were analyzed.
  
  
  RESULTS
  SCC showed a very strong effect in relation to the sampling time and procedure. While the first two points in time (T1; T2) were highly comparable (median fold-change: 0.84; p = 0.7354; correlation ρ = 0.883), patients showed a significant increase (median fold-change: 4.96; p = 0.0017; correlation ρ = -0.036) in concentration when comparing T1 with the sample time subsequent to anesthesia induction (T3). A much weaker increase was found for CYFRA 21-1 at T3 (median fold-change: 1.40; p = 0.0479). The concentration of CEA showed a very small, but systematic decrease (median fold-change: 0.72; p = 0.0039).
  
  
  CONCLUSIONS
  In this study we show the unexpectedly marked influence of blood withdrawal timing (before vs. after anesthesia) and procedure (venous versus arterial vessel puncture) has on the concentration of the protein biomarker SCC and to a less extent upon CYFRA21-1. The potential causes for these effects remain to be elucidated in subsequent studies, however these findings highlight the importance of a standardized, controlled blood collection protocol for biomarker detection.
authors.affiliation: Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany ; Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kahn
authors.affiliation: Roche Diagnostics GmbH, 68305 Mannheim, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Riedlinger
authors.affiliation: Roche Diagnostics GmbH, 68305 Mannheim, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Roeßler
authors.affiliation: Roche Diagnostics GmbH, 68305 Mannheim, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Rabe
authors.affiliation: Center of Thoracic Surgery, Asklepios Fachkliniken München-Gauting, Ludwig Maximilians University, 82131 Gauting, Germany ; Comprehensive Pneumology Centre Munich (CPC-M), German Centre for Lung Research (DZL), Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lindner
authors.affiliation: Center of Thoracic Surgery, Asklepios Fachkliniken München-Gauting, Ludwig Maximilians University, 82131 Gauting, Germany ; Comprehensive Pneumology Centre Munich (CPC-M), German Centre for Lung Research (DZL), Munich, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Koch
authors.affiliation: Center of Thoracic Surgery, Asklepios Fachkliniken München-Gauting, Ludwig Maximilians University, 82131 Gauting, Germany ; Comprehensive Pneumology Centre Munich (CPC-M), German Centre for Lung Research (DZL), Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schott-Hildebrand
authors.affiliation: Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany ; Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Felix J
authors.initials: FJ
authors.lastname: Herth
authors.affiliation: Translational Research Unit (STF), Thoraxklinik, University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany ; Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schneider
authors.affiliation: Translational Research Unit (STF), Thoraxklinik, University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany ; Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
authors.affiliation: Translational Research Unit (STF), Thoraxklinik, University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany ; Translational Lung Research Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Muley
keywords: Anesthesia induction; Biomarker; Blood specimens; CEA; CYFRA 21-1; Lung cancer; SCC; SPREC coding; Sampling time points