TY - JOUR
T1 - Methylation analysis in spontaneous sputum for lung cancer diagnosis
AU - Hubers, A. Jasmijn
AU - van der Drift, Miep A.
AU - Prinsen, Clemens F M
AU - Witte, Birgit I.
AU - Wang, Yinghui
AU - Shivapurkar, Narayan
AU - Stastny, Victor
AU - Bolijn, Anne S.
AU - Hol, Bernard E A
AU - Feng, Ziding
AU - Dekhuijzen, P. N Richard
AU - Gazdar, Adi F.
AU - Thunnissen, Erik
PY - 2014/5
Y1 - 2014/5
N2 - Objectives: Lung cancer is the most fatal cancer in the developed world due to presence of metastases at time of diagnosis. The aim of this study is to examine DNA hypermethylation in sputum compared to sputum cytology for the diagnosis of lung cancer. A novel risk analysis is introduced, using the distinction between diagnostic and risk markers. Methods: Two independent sets were randomly composed from a prospectively collected sputum bank (Set 1: n= 98 lung cancer patients, n= 90 controls; Set 2: n= 60 lung cancer patients, n= 445 controls). Sputum cytology was performed for all samples. The following DNA hypermethylation markers were tested in both sets: RASSF1A, APC and cytoglobin ( CYGB). Two statistical analyses were conducted: multivariate logistic regression and a risk classification model based on post-test probabilities. Results: In multivariate analysis, RASSF1A was the best of the three markers in discriminating lung cancer cases from controls in both sets (sensitivity 41-52%, specificity 94-96%). The risk model showed that 36% of lung cancer patients were defined as "high risk" (≥60% chance on lung cancer) based on RASSF1A hypermethylation in Set 1. The model was reproducible in Set 2. Risk markers ( APC, CYGB) have less diagnostic value.Sensitivity of cytology for lung cancer diagnosis was 22%. RASSF1A hypermethylation yielded a sensitivity of 45%. The combined sensitivity for RASSF1A with cytological diagnosis increased to 52% with similar specificity (94%). Conclusion: In a diagnostic setting, hypermethylation analysis in sputum is possible when a diagnostic marker is used. However, risk markers are insufficient for this purpose.
AB - Objectives: Lung cancer is the most fatal cancer in the developed world due to presence of metastases at time of diagnosis. The aim of this study is to examine DNA hypermethylation in sputum compared to sputum cytology for the diagnosis of lung cancer. A novel risk analysis is introduced, using the distinction between diagnostic and risk markers. Methods: Two independent sets were randomly composed from a prospectively collected sputum bank (Set 1: n= 98 lung cancer patients, n= 90 controls; Set 2: n= 60 lung cancer patients, n= 445 controls). Sputum cytology was performed for all samples. The following DNA hypermethylation markers were tested in both sets: RASSF1A, APC and cytoglobin ( CYGB). Two statistical analyses were conducted: multivariate logistic regression and a risk classification model based on post-test probabilities. Results: In multivariate analysis, RASSF1A was the best of the three markers in discriminating lung cancer cases from controls in both sets (sensitivity 41-52%, specificity 94-96%). The risk model showed that 36% of lung cancer patients were defined as "high risk" (≥60% chance on lung cancer) based on RASSF1A hypermethylation in Set 1. The model was reproducible in Set 2. Risk markers ( APC, CYGB) have less diagnostic value.Sensitivity of cytology for lung cancer diagnosis was 22%. RASSF1A hypermethylation yielded a sensitivity of 45%. The combined sensitivity for RASSF1A with cytological diagnosis increased to 52% with similar specificity (94%). Conclusion: In a diagnostic setting, hypermethylation analysis in sputum is possible when a diagnostic marker is used. However, risk markers are insufficient for this purpose.
KW - Biomarkers
KW - Diagnosis
KW - Early detection
KW - Epigenetics
KW - Methylation
KW - Non-small cell lung cancer
KW - Sputum
UR - http://www.scopus.com/inward/record.url?scp=84899478253&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899478253&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2014.01.019
DO - 10.1016/j.lungcan.2014.01.019
M3 - Article
C2 - 24598366
AN - SCOPUS:84899478253
SN - 0169-5002
VL - 84
SP - 127
EP - 133
JO - Lung Cancer
JF - Lung Cancer
IS - 2
ER -