title: Performance evaluation of the DNA methylation biomarker SHOX2 for the             aid in diagnosis of lung cancer based on the analysis of bronchial aspirates.
abstract: 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.
authors: Epigenomics AG, Berlin, Germany.
authors: Dimo
authors: D
authors: Dietrich
authors: Christoph
authors: C
authors: Kneip
authors: Olaide
authors: O
authors: Raji
authors: Triantafillos
authors: T
authors: Liloglou
authors: Anke
authors: A
authors: Seegebarth
authors: Thomas
authors: T
authors: Schlegel
authors: Nadja
authors: N
authors: Flemming
authors: Sebastian
authors: S
authors: Rausch
authors: Jürgen
authors: J
authors: Distler
authors: Michael
authors: M
authors: Fleischhacker
authors: Bernd
authors: B
authors: Schmidt
authors: Thomas
authors: T
authors: Giles
authors: Martin
authors: M
authors: Walshaw
authors: Chris
authors: C
authors: Warburton
authors: Volker
authors: V
authors: Liebenberg
authors: John K
authors: JK
authors: Field
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001980:Bronchi / Q000378:metabolism; D018893:Bronchoalveolar Lavage / Q000379:methods; D016022:Case-Control Studies; D003429:Cross Reactions; D019175:DNA Methylation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011786:Quality Control; D011933:Reagent Kits, Diagnostic; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D011933:Reagent Kits, Diagnostic; C484664:SHOX2 protein, human