TY - JOUR
T1 - Performance evaluation of the DNA methylation biomarker SHOX2 for the aid in diagnosis of lung cancer based on the analysis of bronchial aspirates
AU - Dietrich, Dimo
AU - Kneip, Christoph
AU - Raji, Olaide
AU - Liloglou, Triantafillos
AU - Seegebarth, Anke
AU - Schlegel, Thomas
AU - Flemming, Nadja
AU - Rausch, Sebastian
AU - Distler, Jürgen
AU - Fleischhacker, Michael
AU - Schmidt, Bernd
AU - Giles, Thomas
AU - Walshaw, Martin
AU - Warburton, Chris
AU - Liebenberg, Volker
AU - Field, John K
PY - 2012/3/1
Y1 - 2012/3/1
N2 - In the identification of subjects with lung cancer, increased DNA methylation of the SHOX2 gene locus in bronchial aspirates has previously been proven to be a clinically valuable biomarker. This is particularly true in cases where the cytological and histological results following bronchoscopy are undetermined. This previous case control study was conducted using research assay components and a complex work flow. To facilitate the use in a diagnostic setting, a CE marked in vitro diagnostic test kit to quantify SHOX2 DNA methylation in bronchial aspirates was developed and characterized. The presented assay for measuring SHOX2 DNA methylation in bronchial aspirates is based on two major steps: generation of bisulfite converted template DNA from patient samples followed by subsequent determination of SHOX2 biomarker methylation by real-time PCR. Individual kits for DNA preparation, real-time PCR analysis and work flow control were developed. This study describes the analytical performance (reproducibility, accuracy, interfering substances, cross-reactivity) of the in vitro diagnostic (IVD) test kit 'Epi proLung BL Reflex Assay'. In addition, the intended use of the test was validated in a clinical performance evaluation (case control) study comprised of 250 patients (125 cases, 125 controls). The results describe the test as a robust and reliable diagnostic tool for identifying patients with lung cancer using Saccomanno-fixed bronchial lavage specimens (AUC [95% confidence intervals] = 0.94 [0.91-0.98], sensitivity 78% [69-86]/specificity 96% [90-99]). This test may be used as a diagnostic adjunct to existing clinical and pathological investigations in lung cancer.
AB - In the identification of subjects with lung cancer, increased DNA methylation of the SHOX2 gene locus in bronchial aspirates has previously been proven to be a clinically valuable biomarker. This is particularly true in cases where the cytological and histological results following bronchoscopy are undetermined. This previous case control study was conducted using research assay components and a complex work flow. To facilitate the use in a diagnostic setting, a CE marked in vitro diagnostic test kit to quantify SHOX2 DNA methylation in bronchial aspirates was developed and characterized. The presented assay for measuring SHOX2 DNA methylation in bronchial aspirates is based on two major steps: generation of bisulfite converted template DNA from patient samples followed by subsequent determination of SHOX2 biomarker methylation by real-time PCR. Individual kits for DNA preparation, real-time PCR analysis and work flow control were developed. This study describes the analytical performance (reproducibility, accuracy, interfering substances, cross-reactivity) of the in vitro diagnostic (IVD) test kit 'Epi proLung BL Reflex Assay'. In addition, the intended use of the test was validated in a clinical performance evaluation (case control) study comprised of 250 patients (125 cases, 125 controls). The results describe the test as a robust and reliable diagnostic tool for identifying patients with lung cancer using Saccomanno-fixed bronchial lavage specimens (AUC [95% confidence intervals] = 0.94 [0.91-0.98], sensitivity 78% [69-86]/specificity 96% [90-99]). This test may be used as a diagnostic adjunct to existing clinical and pathological investigations in lung cancer.
KW - Aged
KW - Aged, 80 and over
KW - Biomarkers, Tumor/genetics
KW - Bronchi/metabolism
KW - Bronchoalveolar Lavage/methods
KW - Case-Control Studies
KW - Cross Reactions
KW - DNA Methylation
KW - Female
KW - Homeodomain Proteins/genetics
KW - Humans
KW - Lung Neoplasms/diagnosis
KW - Male
KW - Middle Aged
KW - Quality Control
KW - Reagent Kits, Diagnostic
KW - Real-Time Polymerase Chain Reaction/methods
KW - Reproducibility of Results
KW - Sensitivity and Specificity
U2 - 10.3892/ijo.2011.1264
DO - 10.3892/ijo.2011.1264
M3 - Article (journal)
C2 - 22108652
SN - 1019-6439
VL - 40
SP - 825
EP - 832
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 3
ER -