TY - JOUR
T1 - SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates
AU - Schmidt, Bernd
AU - Liebenberg, Volker
AU - Dietrich, Dimo
AU - Schlegel, Thomas
AU - Kneip, Christoph
AU - Seegebarth, Anke
AU - Flemming, Nadja
AU - Seemann, Stefanie
AU - Distler, Jürgen
AU - Lewin, Jörn
AU - Tetzner, Reimo
AU - Weickmann, Sabine
AU - Wille, Ulrike
AU - Liloglou, Triantafillos
AU - Raji, Olaide
AU - Walshaw, Martin
AU - Fleischhacker, Michael
AU - Witt, Christian
AU - Field, John K
PY - 2010/11/3
Y1 - 2010/11/3
N2 - BACKGROUND: This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.METHODS: Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.RESULTS: Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).CONCLUSIONS: Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.
AB - BACKGROUND: This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.METHODS: Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.RESULTS: Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).CONCLUSIONS: Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.
KW - Adult
KW - Aged
KW - Biomarkers, Tumor/metabolism
KW - Bronchi/metabolism
KW - Bronchoscopy/methods
KW - Carcinoma/metabolism
KW - Case-Control Studies
KW - DNA Methylation
KW - False Positive Reactions
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Homeodomain Proteins/biosynthesis
KW - Humans
KW - Lung Neoplasms/metabolism
KW - Male
KW - Middle Aged
KW - Nucleic Acid Hybridization
KW - Sensitivity and Specificity
U2 - 10.1186/1471-2407-10-600
DO - 10.1186/1471-2407-10-600
M3 - Article (journal)
C2 - 21047392
SN - 1471-2407
VL - 10
SP - 600
JO - BMC Cancer
JF - BMC Cancer
ER -