Clin Proteomics. 2015 Jul 31;12(1):19. doi: 10.1186/s12014-015-9093-6. eCollection 2015.

Blood-sampling collection prior to surgery may have a significant influence upon biomarker concentrations measured.

Kahn N1, Riedlinger J2, Roeßler M2, Rabe C2, Lindner M3, Koch I3, Schott-Hildebrand S3, Herth FJ1, Schneider MA4, Meister M4, Muley TR4.

Author information

• 1Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany ; Translational LungResearch Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Heidelberg, Germany.
• 2Roche Diagnostics GmbH, 68305 Mannheim, Germany.
• 3Center 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.
• 4Translational Research Unit (STF), Thoraxklinik, University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany ; Translational LungResearch Centre Heidelberg (TLRC-H), German Centre for Lung Research (DZL), Heidelberg, Germany.

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.