SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates.
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.
Universitätsklinik und Poliklinik für Innere Medizin I, Universitätsklinikum Halle (Saale), Halle, Germany.
Bernd
B
Schmidt
Volker
V
Liebenberg
Dimo
D
Dietrich
Thomas
T
Schlegel
Christoph
C
Kneip
Anke
A
Seegebarth
Nadja
N
Flemming
Stefanie
S
Seemann
Jürgen
J
Distler
Jörn
J
Lewin
Reimo
R
Tetzner
Sabine
S
Weickmann
Ulrike
U
Wille
Triantafillos
T
Liloglou
Olaide
O
Raji
Martin
M
Walshaw
Michael
M
Fleischhacker
Christian
C
Witt
John K
JK
Field
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D001999:Bronchoscopy / Q000379:methods; D002277:Carcinoma / Q000378:metabolism; D016022:Case-Control Studies; D019175:DNA Methylation; D005189:False Positive Reactions; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C484664:SHOX2 protein, human